US6066318A - Multi-functional hematopoietic fusion proteins between sequence rearranged C-MPL receptor agonists and other hematopoietic factors - Google Patents

Multi-functional hematopoietic fusion proteins between sequence rearranged C-MPL receptor agonists and other hematopoietic factors Download PDF

Info

Publication number
US6066318A
US6066318A US08/835,162 US83516297A US6066318A US 6066318 A US6066318 A US 6066318A US 83516297 A US83516297 A US 83516297A US 6066318 A US6066318 A US 6066318A
Authority
US
United States
Prior art keywords
xaa
leu
ser
ala
arg
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
US08/835,162
Inventor
Yiqing Feng
Nicholas R. Staten
Charles M. Baum
Neena L. Summers
Maire Helena Caparon
S. Christopher Bauer
Linda L. Zurfluh
John P. McKearn
Barbara K. Klein
Stephen C. Lee
Charles A. McWherter
Judith G. Giri
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
GD Searle LLC
Original Assignee
GD Searle LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from PCT/US1996/015774 external-priority patent/WO1997012985A2/en
Application filed by GD Searle LLC filed Critical GD Searle LLC
Priority to US08/835,162 priority Critical patent/US6066318A/en
Assigned to G.D. SEARLE & CO. reassignment G.D. SEARLE & CO. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BAUM, CHARLES M., BAUER, S. CHRISTOPHER, CAPARON, MAIRE H., FENG, YIQING, GIRI, JUDITH G., KEARN, JOHN P., KLEIN, BARBARA K., LEE, STEPHEN C., MCWHERTER, CHARLES A., STATEN, NICHOLAS R., SUMMERS, NEENA L., ZURFLUH, LINDA L.
Assigned to G.D. SEARLE & CO. reassignment G.D. SEARLE & CO. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BAUM, C., BAUER, S., CAPARON, M., GIRI, J., KLEIN, B., LEE, S., MCKEARN, J., MCWHERTER, C., STATEN, N., SUMMERS, N., YINING, FENG, ZURFLUH, L.
Priority to US09/510,238 priority patent/US6730303B1/en
Application granted granted Critical
Publication of US6066318A publication Critical patent/US6066318A/en
Priority to US10/695,584 priority patent/US20040171115A1/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/5403—IL-3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/524—Thrombopoietin, i.e. C-MPL ligand
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/53—Colony-stimulating factor [CSF]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K2035/124—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells the cells being hematopoietic, bone marrow derived or blood cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
    • C07K2319/75—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones

Definitions

  • the present invention relates to multi-functional hematopoietic receptor agonists.
  • Colony stimulating factors which stimulate the differentiation and/or proliferation of bone marrow cells have generated much interest because of their therapeutic potential for restoring depressed levels of hematopoietic stem cell-derived cells.
  • CSFs in both human and murine systems have been identified and distinguished according to their activities.
  • granulocyte-CSF G-CSF
  • macrophage-CSF M-CSF
  • GM-CSF and interleukin-3 IL-3 have broader activities and stimulate the formation of both macrophage, neutrophilic and eosinophilic granulocyte colonies.
  • IL-3 also stimulates the formation of mast, megakaryocyte and pure and mixed erythroid colonies.
  • U.S. Pat. No. 4,877,729 and U.S. Pat. No. 4,959,455 disclose human IL-3 and gibbon IL-3 cDNAs and the protein sequences for which they code.
  • the hIL-3 disclosed has serine rather than proline at position 8 in the protein sequence.
  • PCT International Patent Application
  • WO 88/00598 discloses gibbon- and human-like IL-3.
  • the hIL-3 contains a Ser 8 ->Pro 8 replacement. Suggestions are made to replace Cys by Ser, thereby breaking the disulfide bridge, and to replace one or more amino acids at the glycosylation sites.
  • U.S. Pat. No. 4,810,643 discloses the DNA sequence encoding human G-CSF.
  • WO 91/02754 discloses a fusion protein comprised of GM-CSF and IL-3 which has increased biological activity compared to GM-CSF or IL-3 alone. Also disclosed are nonglycosylated IL-3 and GM-CSF analog proteins as components of the multi-functional hematopoietic receptor agonist.
  • WO 92/04455 discloses fusion proteins composed of IL-3 fused to a lymphokine selected from the group consisting of IL-3, IL-6, IL-7, IL-9, IL-11, EPO and G-CSF.
  • WO 95/21197 and WO 95/21254 disclose fusion proteins capable of broad multi-functional hematopoietic properties.
  • GB 2,285,446 relates to the c-mpl ligand (thrombopoietin) and various forms of thrombopoietin which are shown to influence the replication, differentiation and maturation of megakaryocytes and megakaryocytes progenitors which may be used for the treatment of thrombocytopenia.
  • EP 675,201 A1 relates to the c-mpl ligand (Megakaryocyte growth and development factor (MGDF), allelic variations of c-mpl ligand and c-mpl ligand attached to water soluble polymers such as polyethylene glycol.
  • MGDF Megakaryocyte growth and development factor
  • WO 95/21920 provides the murine and human c-mpl ligand and polypeptide fragments thereof.
  • the proteins are useful for in vivo and ex vivo therapy for stimulating platelet production.
  • the new sequence is joined, either directly or through an additional portion of sequence (linker), to an amino acid that is at or near the original N-terminus, and the new sequence continues with the same sequence as the original until it reaches a point that is at or near the amino acid that was N-terminal to the breakpoint site of the original sequence, this residue forming the new C-terminus of the chain.
  • linker an additional portion of sequence
  • proteins which range in size from 58 to 462 amino acids (Goldenberg & Creighton, J. Mol. Biol. 165: 407-413, 1983; Li & Coffino, Mol. Cell. Biol. 13: 2377-2383, 1993).
  • the proteins examined have represented a broad range of structural classes, including proteins that contain predominantly ⁇ -helix (interleukin-4; Kreitman et al., Cytokine 7: 311-318, 1995), ⁇ -sheet (interleukin-1; Horlick et al., Protein Eng.
  • sequence rearranged protein appeared to have many nearly identical properties as its natural counterpart (basic pancreatic trypsin inhibitor, T4 lysozyme, ribonuclease T1, Bacillus ⁇ -glucanase, interleukin-1 ⁇ , ⁇ -spectrin SH3 domain, pepsinogen, interleukin-4).
  • the positions of the internal breakpoints used in the studies cited here are found exclusively on the surface of proteins, and are distributed throughout the linear sequence without any obvious bias towards the ends or the middle (the variation in the relative distance from the original N-terminus to the breakpoint is ca. 10 to 80% of the total sequence length).
  • the linkers connecting the original N- and C-termini in these studies have ranged from 0 to 9 residues. In one case (Yang & Schachman, Proc. Natl. Acad. Sci. U.S.A. 90: 11980-11984, 1993), a portion of sequence has been deleted from the original C-terminal segment, and the connection made from the truncated C-terminus to the original N-terminus.
  • Novel hematopoietic proteins of this invention are represented by the formulas:
  • R 1 and R 2 are independently selected from the group consisting of;
  • Xaa at position 1 is Thr, Ser, Arg, Tyr or Gly;
  • Xaa at position 2 is Pro or Leu
  • Xaa at position 3 is Leu, Arg, Tyr or Ser;
  • Xaa at position 13 is Phe, Ser, His, Thr or Pro;
  • Xaa at position 16 is Lys, Pro, Ser, Thr or His;
  • Xaa at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg;
  • Xaa at position 18 is Leu, Thr, Pro, His, Ile or Cys
  • Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala;
  • Xaa at position 24 is Ile, Pro, Tyr or Leu;
  • Xaa at position 27 is Asp, or Gly;
  • Xaa at position 30 is Ala, Ile, Leu or Gly;
  • Xaa at position 34 is Lys or Ser
  • Xaa at position 36 is Cys or Ser
  • Xaa at position 42 is Cys or Ser
  • Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu;
  • Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln, or Thr;
  • Xaa at position 46 is Glu, Arg, Phe, Arg, Ile or Ala;
  • Xaa at position 47 is Leu or Thr
  • Xaa at position 49 is Leu, Phe, Arg or Ser;
  • Xaa at position 50 is Leu, Ile, His, Pro or Tyr;
  • Xaa at position 54 is Leu or His
  • Xaa at position 64 is Cys or Ser
  • Xaa at position 67 is Gln, Lys, Leu or Cys;
  • Xaa at position 70 is Gln, Pro, Leu, Arg or Ser;
  • Xaa at position 74 is Cys or Ser
  • Xaa at position 104 is Asp, Gly or Val
  • Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly;
  • Xaa at position 115 is Thr, His, Leu or Ala
  • Xaa at position 120 is Gln, Gly, Arg, Lys or His
  • Xaa at position 123 is Glu, Arg, Phe or Thr
  • Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu;
  • Xaa at position 146 is Arg or Gln;
  • Xaa at position 147 is Arg or Gln;
  • Xaa at position 156 is His, Gly or Ser;
  • Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly;
  • Xaa at position 162 is Glu, Leu, Gly or Trp;
  • Xaa at position 163 is Val, Gly, Arg or Ala;
  • Xaa at position 169 is Arg, Ser, Leu, Arg or Cys;
  • Xaa at position 170 is His, Arg or Ser;
  • N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;
  • Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
  • Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
  • Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
  • Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
  • Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
  • Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
  • Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
  • Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
  • Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
  • Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
  • Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
  • Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
  • Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
  • Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
  • Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
  • Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
  • Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
  • Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
  • Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
  • Xaa at position 36 is Asp, Leu, or Val
  • Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
  • Xaa at position 38 is Asn, or Ala
  • Xaa at position 40 is Leu, Trp, or Arg;
  • Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
  • Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
  • Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
  • Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
  • Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
  • Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
  • Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
  • Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
  • Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
  • Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
  • Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
  • Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
  • Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
  • Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
  • Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
  • Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
  • Xaa at position 57 is Asn or Gly;
  • Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
  • Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
  • Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
  • Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
  • Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
  • Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
  • Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
  • Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
  • Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
  • Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
  • Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
  • Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
  • Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
  • Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
  • Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
  • Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
  • Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
  • Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
  • Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
  • Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
  • Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
  • Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
  • Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
  • Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
  • Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
  • Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
  • Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
  • Xaa at position 85 is Leu, Asn, Val, or Gln;
  • Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
  • Xaa at position 87 is Leu, Ser, Trp, or Gly;
  • Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
  • Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
  • Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
  • Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
  • Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
  • Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
  • Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
  • Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
  • Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
  • Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
  • Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
  • Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
  • Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
  • Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln;
  • Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
  • Xaa at position 103 is Asp, or Ser;
  • Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
  • Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
  • Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
  • Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
  • Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
  • Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp;
  • Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
  • Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
  • Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
  • Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
  • Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
  • Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;
  • Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
  • Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
  • Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
  • Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
  • Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
  • Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
  • amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3;
  • N-terminus is joined to the C-terminus directly or through a linker (L 2 ) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;
  • Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met;
  • Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
  • Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
  • Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn;
  • N-terminus is joined to the C-terminus directly or through a linker (L 2 ) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;
  • Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
  • Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
  • Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
  • Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
  • Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
  • Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
  • Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
  • Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
  • Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
  • Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
  • Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
  • Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
  • Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
  • Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
  • Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
  • Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
  • Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
  • Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
  • Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
  • Xaa at position 36 is Asp, Leu, or Val
  • Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
  • Xaa at position 38 is Asn, or Ala
  • Xaa at position 40 is Leu, Trp, or Arg;
  • Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
  • Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
  • Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
  • Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
  • Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
  • Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
  • Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
  • Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
  • Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
  • Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
  • Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
  • Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
  • Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or
  • Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
  • Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
  • Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
  • Xaa at position 57 is Asn or Gly;
  • Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
  • Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
  • Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
  • Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
  • Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
  • Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
  • Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
  • Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
  • Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
  • Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
  • Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
  • Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
  • Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
  • Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
  • Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
  • Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
  • Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
  • Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
  • Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
  • Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
  • Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
  • Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
  • Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
  • Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
  • Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
  • Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
  • Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
  • Xaa at position 85 is Leu, Asn, Val, or Gln;
  • Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
  • Xaa at position 87 is Leu, Ser, Trp, or Gly;
  • Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
  • Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
  • Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
  • Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
  • Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
  • Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
  • Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
  • Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
  • Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
  • Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
  • Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
  • Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
  • Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
  • Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln;
  • Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
  • Xaa at position 103 is Asp, or Ser;
  • Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
  • Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
  • Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
  • Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
  • Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
  • Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp;
  • Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
  • Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
  • Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
  • Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
  • Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
  • Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;
  • Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
  • Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
  • Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
  • Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
  • Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
  • Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
  • Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
  • amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; or
  • L 1 is a linker capable of linking R 1 to R 2 ;
  • R 1 or R 2 is selected from the polypeptide of formula (I) , (II), or (III);
  • said hematopoietic protein can optionally be immediately preceded by (methionine -1 ), (alanine -1 ) or (methionine -2 , alanine -1 ).
  • breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (I) above are; 38-39, 39-40, 40-41, 41-42, 48-49, 53-54, 54-55, 55-56, 56-57, 57-58, 58-59, 59-60, 60-61, 61-62, 62-63, 64-65, 65-66, 66-67, 67-68, 68-69, 69-70, 96-97, 125-126, 126-127, 127-128, 128-129, 129-130, 130-131, 131-132, 132-133, 133-134, 134-135, 135-136, 136-137, 137-138, 138-139, 139-140, 140-141 and 141-142.
  • breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (I) above are; 38-39, 48-49, 96-97, 125-126, 132-133 and 141-142.
  • breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (II) above are; 28-29, 29-30, 30-31, 31-32, 32-33, 33-34, 34-35, 35-36, 36-37, 37-38, 38-39, 39-40, 66-67, 67-68, 68-69, 69-70, 70-71, 84-85, 85-86, 86-87, 87-88, 88-89, 89-90, 90-91, 98-99, 99-100, 100-101 and 101-102.
  • breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (II) above are; 34-35, 69-70 and 90-91.
  • breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (III) above or the amino acid sequence of (SEQ ID NO:256) are; 80-81, 81-82, 82-83, 83-84, 84-85, 85-86, 86-87, 108-109, 109-110, 110-111, 111-112, 112-113, 113-114, 114-115, 115-116, 116-117, 117-118, 118-119, 119-120, 120-121, 121-122, 122-123, 123-124, 124-125, 125-126 and 126-127.
  • breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (III) above or the amino acid sequence of (SEQ ID NO:256) are; 81-82, 108-109, 115-116, 119-120, 122-123 and 125-126.
  • the invention is also intended to include multifunctional receptor agonists which comprises a sequence rearranged c-mpl receptor agonist in which the cysteine at position 7 and/or 151 are substituted with another amino acid.
  • the substitution at position 7 and 151 is Ser, Ala, Gly, His, Asn, Asp, Thr, Phe or Thr. More preferably, the substitution at position 7 and 151 is Ser, Ala, Gly, His or Asn.
  • the multifunctional receptor agonist of the present invention can also be represented by the following formula:
  • X 1 is a peptide comprising an amino acid sequence corresponding to the sequence of residues n+1 through J of the original protein having amino acids residues numbered sequentially 1 through J with an amino terminus at residue 1;
  • L is an optional linker
  • X 2 is a peptide comprising an amino acid sequence of residues 1 through n of the original protein
  • Y 2 is a peptide comprising an amino acid sequence of residues 1 through n of the original protein
  • L 1 and L 2 are optional peptide spacers:
  • n is an integer ranging from 1 to J-1;
  • b, c, and d are each independently 0 or 1;
  • a and e are either 0 or 1, provided that both a and e cannot both be 0;
  • T 1 and T 2 are proteins.
  • the present invention relates to recombinant expression vectors comprising nucleotide sequences encoding the multi-functional hematopoietic receptor agonists, related microbial expression systems, and processes for making the multi-functional hematopoietic receptor agonists.
  • the invention also relates to pharmaceutical compositions containing the multi-functional hematopoietic receptor agonists, and methods for using the multi-functional hematopoietic receptor agonists.
  • in vitro uses would include the ability to stimulate bone marrow and blood cell activation and growth before infusion into patients.
  • FIG. 1 schematically illustrates the sequence rearrangement of a protein.
  • the N-terminus (N) and the C-terminus (C) of the native protein are joined through a linker, or joined directly.
  • the protein is opened at a breakpoint creating a new N-terminus (new N) and a new C-terminus (new-C) resulting in a protein with a new linear amino acid sequence.
  • a rearranged molecule may be synthesized de novo as linear molecule and not go through the steps of joining the original N-terminus and the C-terminus and opening of the protein at the breakpoint.
  • FIG. 2 shows a schematic of Method I, for creating new proteins in which the original N-terminus and C-terminus of the native protein are joined with a linker and different N-terminus and C-terminus of the protein are created.
  • the sequence rearrangement results in a new gene encoding a protein with a new N-terminus created at amino acid 97 of the original protein, the original C-terminus (a.a. 174) joined to the amino acid 11 (a.a. 1-10 are deleted) through a linker region and a new C-terminus created at amino acid 96 of the original sequence.
  • FIG. 3 shows a schematic of Method II, for creating new proteins in which the original N-terminus and C-terminus of the native protein are joined without a linker and different N-terminus and C-terminus of the protein are created.
  • the sequence rearrangement results in a new gene encoding a protein with a new N-terminus created at amino acid 97 of the original protein, the original C-terminus (a.a. 174) joined to the original N-terminus and a new C-terminus created at amino acid 96 of the original sequence.
  • FIG. 4 shows a schematic of Method III, for creating new proteins in which the original N-terminus and C-terminus of the native protein are joined with a linker and different N-terminus and C-terminus of the protein are created.
  • the sequence rearrangement results in a new gene encoding a protein with a new N-terminus created at amino acid 97 of the original protein, the original C-terminus (a.a. 174) joined to amino acid 1 through a linker region and a new C-terminus created at amino acid 96 of the original sequence.
  • the present invention encompasses multi-functional hematopoietic receptor agonists formed from covalently linked polypeptides, each of which may act through a different and specific cell receptor to initiate complementary biological activities.
  • Hematopoiesis requires a complex series of cellular events in which stem cells generate continuously into large populations of maturing cells in all major lineages.
  • regulators with hematopoietic proliferative activity There are currently at least 20 known regulators with hematopoietic proliferative activity. Most of these proliferative regulators can only stimulate one or another type of colony formation in vitro, the precise pattern of colony formation stimulated by each regulator is quite distinctive. No two regulators stimulate exactly the same pattern of colony formation, as evaluated by colony numbers or, more importantly, by the lineage and maturation pattern of the cells making up the developing colonies.
  • Proliferative responses can most readily be analyzed in simplified in vitro culture systems. Three quite different parameters can be distinguished: alteration in colony size, alteration in colony numbers and cell lineage. Two or more factors may act on the progenitor cell, inducing the formation of larger number of progeny thereby increasing the colony size. Two or more factors may allow increased number of progenitor cells to proliferate either because distinct subsets of progenitors cells exist that respond exclusively to one factor or because some progenitors require stimulation by two or more factors before being able to respond.
  • Activation of additional receptors on a cell by the use of two or more factors is likely to enhance the mitotic signal because of coalescence of initially differing signal pathways into a common final pathway reaching the nucleus (Metcalf, Nature 339: 27, 1989).
  • Other mechanisms could explain synergy. For example, if one signaling pathway is limited by an intermediate activation of an additional signaling pathway which is caused by a second factor, then this may result in a super additive response.
  • activation of one receptor type can induce an enhanced expression of other receptors (Metcalf, Blood 82: 3515-3523, 1993).
  • Two or more factors may result in a different pattern of cell lineages than from a single factor.
  • the use of multi-functional hematopoietic receptor agonists may have a potential clinical advantage resulting from a proliferative response that is not possible by any single factor.
  • tyrosine kinase receptors including those for epidermal growth factor, M-CSF (Sherr, Blood 75: 1, 1990) and SCF (Yarden et al., EMBO J. 6: 3341, 1987): and (2) hematopoietic receptors, not containing a tyrosine kinase domain, but exhibiting obvious homology in their extracellular domain (Bazan, PNAS USA 87: 6934-6938, 1990).
  • EPO erythropoietin
  • GM-CSF Gearing et al., EMBO J. 8: 3667, 1989
  • IL-3 Kitamura et al., Cell 66: 1165, 1991
  • G-CSF Fukunaga et al., J. Bio. Chem. 265: 14008-15, 1990
  • IL-4 Harada et al., PNAS USA 87: 857, 1990
  • IL-5 Takaki et al., EMBO J.
  • IL-6 Yamamoto et al., Science 241: 825, 1988
  • IL-7 Goodwin et al., Cell 60: 941-51, 1990
  • LIF Faring et al., EMBO J. 10: 2839, 1991
  • IL-2 Cosman et al., Mol-Immunol. 23: 935-94, 1986.
  • Most of the latter group of receptors exists in a high-affinity form as heterodimers. After ligand binding, the specific ⁇ -chains become associated with at least one other receptor chain ( ⁇ -chain, ⁇ -chain). Many of these factors share a common receptor subunit.
  • the ⁇ -chains for GM-CSF, IL-3 and IL-5 share the same ⁇ -chain (Kitamura et al., Cell 66: 1165, 1991), Takaki et al., EMBO J. 10: 2833-8, 1991) and receptor complexes for IL-6, LIF and IL-11 share a common ⁇ -chain (gp130) (Taga et al., Cell 58: 573-81, 1989; Gearing et al., Science 255: 1434-7, 1992).
  • the receptor complexes of IL-2, IL-4, IL-7, IL-9 and IL-15 share a common ⁇ -chain (Kondo et al., Science 262: 1874, 1993; Russell et al., Science 266: 1042-1045, 1993; Noguchi et al., Science 262: 1877, 1993; Giri et al., EMBO J. 13: 2822-2830, 1994).
  • the use of a multiply acting hematopoietic factor may also have a potential advantage by reducing the demands placed on factor-producing cells and their induction systems. If there are limitations in the ability of a cell to produce a factor, then by lowering the required concentrations of each of the factors, and using them in combination may usefully reduce demands on the factor-producing cells.
  • the use of a multiply acting hematopoietic factor may lower the amount of the factors that would be needed, probably reducing the likelihood of adverse side-effects.
  • Novel compounds of this invention are represented by a formula selected from the group consisting of:
  • R 1 and R2 are as defined above.
  • R 2 is preferably a colony stimulating factor with a different but complementary activity than R 1 .
  • complementary activity is meant activity which enhances or changes the response to another cell modulator.
  • the R 1 polypeptide is joined either directly or through a linker segment to the R 2 polypeptide.
  • the term "directly" defines multi-functional hematopoietic receptor agonists in which the polypeptides are joined without a peptide linker.
  • L 1 represents a chemical bond or polypeptide segment to which both R 1 and R 2 are joined in frame
  • L 1 is a linear peptide to which R 1 and R 2 are joined by amide bonds linking the carboxy terminus of R 1 to the amino terminus of L 1 and carboxy terminus of L 1 to the amino terminus of R 2 .
  • joined in frame is meant that there is no translation termination or disruption between the reading frames of the DNA encoding R 1 and R 2 .
  • colony stimulating factors are cytokines, lymphokines, interleukins, hematopoietic growth factors which can be joined to (I), (II) or (III) include GM-CSF, G-CSF, c-mpl ligand (also known as TPO or MGDF), M-CSF, erythropoietin (EPO), IL-1, IL-4, IL-2, IL-3, IL-5, IL 6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-15, LIF, flt3 ligand, human growth hormone, and stem cell factor (SCF) also known as steel factor or c-kit ligand.
  • SCF stem cell factor
  • this invention encompasses the use of modified R 1 or R 2 molecules or mutated or modified DNA sequences encoding these R 1 or R 2 molecules.
  • the present invention also includes multi-functional hematopoietic receptor agonists in which R 1 or R 2 is an hIL-3 variant, c-mpl ligand variant, or G-CSF variant.
  • a "hIL-3 variant” is defined as a hIL-3 molecule which has amino acid substitutions and/or portions of hIL-3 deleted as disclosed in WO 94/12638, WO 94/12639 and WO 95/00646, as well as other variants known in the art.
  • a "c-mpl ligand variant” is defined an c-mpl ligand molecule which has amino acid substitutions and/or portions of c-mpl ligand deleted, disclosed in U.S. application Ser. No. 08/383,035 as well as other variants known in the art.
  • a "G-CSF variant” is defined an G-CSF molecule which has amino acid substitutions and/or portions of G-CSF deleted, as disclosed herein, as well as other variants known in the art.
  • the linking group (Li) is generally a polypeptide of between 1 and 500 amino acids in length.
  • the linkers joining the two molecules are preferably designed to (1) allow the two molecules to fold and act independently of each other, (2) not have a propensity for developing an ordered secondary structure which could interfere with the functional domains of the two proteins, (3) have minimal hydrophobic characteristics which could interact with the functional protein domains and (4) provide steric separation of R 1 and R 2 such that R 1 and R 2 could interact simultaneously with their corresponding receptors on a single cell.
  • surface amino acids in flexible protein regions include Gly, Asn and Ser. Virtually any permutation of amino acid sequences containing Gly, Asn and Ser would be expected to satisfy the above criteria for a linker sequence.
  • Thr and Ala may also be used in the linker sequence. Additional amino acids may also be included in the linkers due to the addition of unique restriction sites in the linker sequence to facilitate construction of the multi-functional hematopoietic receptor agonists.
  • Preferred L 1 linkers of the present invention include sequences selected from the group of formulas: (Gly 3 Ser) n (SEQ ID NO:4), (Gly 4 Ser) n (SEQ ID NO:5), (Gly 5 Ser) n (SEQ ID NO:6), (Gly n Ser) n (SEQ ID NO:7) or (AlaGlySer) n (SEQ ID NO:8).
  • a highly-flexible linker is the glycine and serine-rich spacer region present within the pIII protein of the filamentous bacteriophages, e.g. bacteriophages M13 or fd (Schaller et al., PNAS USA 72: 737-741, 1975).
  • This region provides a long, flexible spacer region between two domains of the pIII surface protein.
  • the spacer region consists of the amino acid sequence:
  • the present invention also includes linkers in which an endopeptidase recognition sequence is included.
  • a cleavage site may be valuable to separate the individual components of the multi-functional hematopoietic receptor agonist to determine if they are properly folded and active in vitro.
  • various endopeptidases include, but are not limited to, plasmin, enterokinase, kallikrein, urokinase, tissue plasminogen activator, clostripain, chymosin, collagenase, Russell's viper venom protease, postproline cleavage enzyme, V8 protease, Thrombin and factor Xa.
  • Peptide linker segments from the hinge region of heavy chain immunoglobulins IgG, IgA, IgM, IgD or IgE provide an angular relationship between the attached polypeptides. Especially useful are those hinge regions where the cysteines are replaced with serines.
  • Preferred linkers of the present invention include sequences derived from murine IgG gamma 2b hinge region in which the cysteines have been changed to serines. These linkers may also include an endopeptidase cleavage site. Examples of such linkers include the following sequences:
  • the present invention is, however, not limited by the form, size or number of linker sequences employed and the only requirement of the linker is that functionally it does not interfere with the folding and function of the individual molecules of the multi-functional hematopoietic receptor agonist.
  • One aspect of the invention includes multi-functional hematopoietic receptor agonists which comprise a sequence rearranged c-mpl receptor agonist in which the cysteine(s) at position 7 and 151 of c-mpl ligand, have been substituted with another amino acid.
  • Kaushansky et al. (Blood 86: 255a Abstract 1008, 1995) teaches that all four of the cysteines at positions 7, 29, 85, and 151 are required for bioactivity.
  • the presence of cysteines in a protein can cause problems in processing when the protein is being produced recombinantly in a bacterial host. Microbially produced cysteine-containing proteins may tend to form multimers which greatly complicate purification of the protein product.
  • a molecule in which a pair of cysteines at positions 7 and 151 are substituted with another amino acid may have one or more advantages including, but not limited to: 1) increased folding efficiency of the heterologously expressed protein; 2) elimination of mispaired disulfides, 3) use of milder refold conditions (ie. Guanidine vs. Urea); 4) increased purification yields, 5) increased protein solubility; and 6) increased protein stability.
  • the length of the amino acid sequence of the linker L 2 to be used in R 1 and/or R 2 can be selected empirically or with guidance from structural information, or by using a combination of the two approaches.
  • a small series of linkers can be prepared for testing using a design whose length is varied in order to span a range from 0 to 50 ⁇ and whose sequence is chosen in order to be consistent with surface exposure (hydrophilicity, Hopp & Woods, Mol. Immunol. 20: 483-489, 1983), Kyte & Doolittle, J. Mol. Biol. 157: 105-132; solvent exposed surface area, Lee & Richards, J. Mol. Biol. 55: 379-400, 1971) and the ability to adopt the necessary conformation with out deranging the conformation of R 1 or R 2 (conformationally flexible; Karplus & Schulz, Naturwissenschaften 72: 212-213, 1985).
  • linkers may be composed of the original sequence, shortened or lengthened as necessary, and when lengthened the additional residues may be chosen to be flexible and hydrophilic as described above; or optionally the original sequence may be substituted for using a series of linkers, one example being the Gly-Gly-Gly-Ser (SEQ ID NO:12) cassette approach mentioned above; or optionally a combination of the original sequence and new sequence having the appropriate total length may be used.
  • Sequences of R 1 and R 2 capable of folding to biologically active states can be prepared by appropriate selection of the beginning (amino terminus) and ending (carboxyl terminus) positions from within the original polypeptide chain while using the linker sequence L 2 as described above.
  • Amino and carboxyl termini are selected from within a common stretch of sequence, referred to as a breakpoint region, using the guidelines described below.
  • a novel amino acid sequence is thus generated by selecting amino and carboxyl termini from within the same breakpoint region. In many cases the selection of the new termini will be such that the original position of the carboxyl terminus immediately preceded that of the amino terminus. However, those skilled in the art will recognize that selections of termini anywhere within the region may function, and that these will effectively lead to either deletions or additions to the amino or carboxyl portions of the new sequence.
  • Examples of structural information that are relevant to the identification of breakpoint regions include the location and type of protein secondary structure (alpha and 3-10 helices, parallel and anti-parallel beta sheets, chain reversals and turns, and loops; Kabsch & Sander, Biopolymers 22: 2577-2637, 1983), the degree of solvent exposure of amino acid residues, the extent and type of interactions of residues with one another (Chothia, Ann. Rev. Biochem. 53: 537-572, 1984) and the static and dynamic distribution of conformations along the polypeptide chain (Alber & Mathews, Methods Enzymol. 154: 511-533, 1987).
  • additional information is known about solvent exposure of residues; one example is a site of post-translational attachment of carbohydrate which is necessarily on the surface of the protein.
  • methods are also available to analyze the primary amino acid sequence in order to make predictions of protein tertiary and secondary structure, solvent accessibility and the occurrence of turns and loops.
  • Biochemical methods are also sometimes applicable for empirically determining surface exposure when direct structural methods are not feasible; for example, using the identification of sites of chain scission following limited proteolysis in order to infer surface exposure (Gentile & Salvatore, Eur. J. Biochem.
  • regions of amino acid sequence that are observed or predicted to have a low degree of solvent exposure are more likely to be part of the so-called hydrophobic core of the protein and should also be avoided for selection of amino and carboxyl termini.
  • those regions that are known or predicted to be in surface turns or loops, and especially those regions that are known not to be required for biological activity are the preferred sites for location of the extremes of the polypeptide chain. Continuous stretches of amino acid sequence that are preferred based on the above criteria are referred to as a breakpoint region.
  • R 1 and R 2 are as is defined above. Domains C 1 and C 2 are either identical or non-identical chemical structures, typically proteinaceous, which can form a non-covalent, specific association. Complexes between C 1 and C 2 result in a one-to-one stoichiometric relationship between R 1 and R 2 for each complex. Examples of domains which associate are "leucine zipper" domains of transcription factors, dimerization domains of bacterial transcription repressors and immunoglobulin constant domains. Covalent bonds link R 1 and C 1 , and R 2 and C 2 , respectively. As indicated in the formulae, the domains C 1 and C 2 can be present either at the N-terminus or C-terminus of their corresponding hematopoietic growth factor (R).
  • R hematopoietic growth factor
  • C 1 and C 2 include those derived from the bZIP family of proteins (Abel et al., Nature 341: 24-25, 1989; Landshulz et al., Science 240: 1759-1764, 1988; Pu et al., Nuc. Acid Res.
  • Preferred multi-functional hematopoietic receptor agonists of the present invention include colony stimulating factors dimerized by virtue of their incorporation as translational multi-functional hematopoietic receptor agonists with the leucine zipper dimerization domains of the bZIP family proteins Fos and Jun.
  • the leucine zipper domain of Jun is capable of interacting with identical domains.
  • the leucine zipper domain of Fos interacts with the Jun leucine zipper domain, but does not interact with other Fos leucine zipper domains. Mixtures of Fos and Jun predominantly result in formation of Fos-Jun heterodimers. Consequently, when joined to colony stimulating factors, the Jun domain can be used to direct the formation of either homo- or heterodimers. Preferential formation of heterodimers can be achieved if one of the colony stimulating factor partners is engineered to possess the Jun leucine zipper domain while the other is engineered to possess the Fos zipper.
  • Additional peptide sequences may also be added to facilitate purification or identification of multi-functional hematopoietic receptor agonist proteins (e.g., poly-His).
  • a highly antigenic peptide may also be added that would enable rapid assay and facile purification of the multi-functional hematopoietic receptor agonist protein by a specific monoclonal antibody.
  • mutant amino acid sequence refers to a polypeptide having an amino acid sequence which varies from a native sequence due to amino acid deletions, substitutions, or both, or is encoded by a nucleotide sequence intentionally made variant from a native sequence.
  • Native sequence refers to an amino acid or nucleic acid sequence which is identical to a wild-type or native form of a gene or protein.
  • Hematopoietic growth factors can be characterized by their ability to stimulate colony formation by human hematopoietic progenitor cells.
  • the colonies formed include erythroid, granulocyte, megakaryocyte, granulocytic macrophages and mixtures thereof.
  • Many of the hematopoietic growth factors have demonstrated the ability to restore bone marrow function and peripheral blood cell populations to therapeutically beneficial levels in studies performed initially in primates and subsequently in humans. Many or all of these biological activities of hematopoietic growth factors involve signal transduction and high affinity receptor binding.
  • Multi-functional hematopoietic receptor agonists of the present invention may exhibit useful properties such as having similar or greater biological activity when compared to a single factor or by having improved half-life or decreased adverse side effects, or a combination of these properties.
  • Multi-functional hematopoietic receptor agonists which have little or no agonist activity maybe useful as antagonists, as antigens for the production of antibodies for use in immunology or immunotherapy, as genetic probes or as intermediates used to construct other useful hIL-3 muteins.
  • Biological activity of the multi-functional hematopoietic receptor agonist proteins of the present invention can be determined by DNA synthesis in factor-dependent cell lines or by counting the colony forming units in an in vitro bone marrow assay.
  • the multi-functional hematopoietic receptor agonists of the present invention may have an improved therapeutic profile as compared to single acting hematopoietic agonists.
  • some multi-functional hematopoietic receptor agonists of the present invention may have a similar or more potent growth factor activity relative to other hematopoietic agonists without having a similar or corresponding increase in side-effects.
  • the present invention also includes the DNA sequences which code for the multi-functional hematopoietic receptor agonist proteins, DNA sequences which are substantially similar and perform substantially the same function, and DNA sequences which differ from the DNAs encoding the multi-functional hematopoietic receptor agonists of the invention only due to the degeneracy of the genetic code. Also included in the present invention are the oligonucleotide intermediates used to construct the mutant DNAs and the polypeptides coded for by these oligonucleotides.
  • Pairs of complementary synthetic oligonucleotides encoding the desired gene can be made and annealed to each other.
  • the DNA sequence of the oligonucleotide would encode sequence for amino acids of desired gene with the exception of those substituted and/or deleted from the sequence.
  • Plasmid DNA can be treated with the chosen restriction endonucleases then ligated to the annealed oligonucleotides.
  • the ligated mixtures can be used to transform competent JM101 cells to resistance to an appropriate antibiotic.
  • Single colonies can be picked and the plasmid DNA examined by restriction analysis and/or DNA sequencing to identify plasmids with the desired genes.
  • Cloning of the DNA sequences of the novel multifunctional hematopoietic agonists wherein at least one of the with the DNA sequence of the other colony stimulating factor may be accomplished by the use of intermediate vectors.
  • one gene can be cloned directly into a vector containing the other gene.
  • Linkers and adapters can be used for joining the DNA sequences, as well as replacing lost sequences, where a restriction site was internal to the region of interest.
  • genetic material (DNA) encoding one polypeptide, peptide linker, and the other polypeptide is inserted into a suitable expression vector which is used to transform bacteria, yeast, insect cells or mammalian cells.
  • the transformed organism is grown and the protein isolated by standard techniques.
  • the resulting product is therefore a new protein which has a colony stimulating factor joined by a linker region to a second colony stimulating factor.
  • Another aspect of the present invention provides plasmid DNA vectors for use in the expression of these novel multi-functional hematopoietic receptor agonists.
  • These vectors contain the novel DNA sequences described above which code for the novel polypeptides of the invention.
  • Appropriate vectors which can transform microorganisms capable of expressing the multi-functional hematopoietic receptor agonists include expression vectors comprising nucleotide sequences coding for the multi-functional hematopoietic receptor agonists joined to transcriptional and translational regulatory sequences which are selected according to the host cells used.
  • Vectors incorporating modified sequences as described above are included in the present invention and are useful in the production of the multi-functional hematopoietic receptor agonist polypeptides.
  • the vector employed in the method also contains selected regulatory sequences in operative association with the DNA coding sequences of the invention and which are capable of directing the replication and expression thereof in selected host cells.
  • a method for producing the novel multi-functional hematopoietic receptor agonists involves culturing suitable cells or cell line, which has been transformed with a vector containing a DNA sequence coding for expression of a novel multi-functional hematopoietic receptor agonist.
  • suitable cells or cell lines may be bacterial cells.
  • E. coli the various strains of E. coli are well-known as host cells in the field of biotechnology. Examples of such strains include E. coli strains JM101 (Yanish-Perron et al.
  • the gene encoding the multi-functional hematopoietic receptor agonists of the present invention may also be constructed such that at the 5' end of the gene codons are added to encode Met -2 -Ala -1 - or Met -1 at the N-terminus of the protein.
  • the N termini of proteins made in the cytoplasm of E. coli are affected by post-translational processing by methionine aminopeptidase (Ben Bassat et al., J. Bac. 169: 751-757, 1987) and possibly by other peptidases so that upon expression the methionine is cleaved off the N-terminus.
  • the multi-functional hematopoietic receptor agonists of the present invention may include multi-functional hematopoietic receptor agonist polypeptides having Met -1 , Ala -1 or Met -2 -Ala -1 at the N-terminus. These mutant multi-functional hematopoietic receptor agonists may also be expressed in E. coli by fusing a secretion signal peptide to the N-terminus. This signal peptide is cleaved from the polypeptide as part of the secretion process.
  • mammalian cells such as Chinese hamster ovary cells (CHO).
  • CHO Chinese hamster ovary cells
  • An expression vector is constructed in which a strong promoter capable of functioning in mammalian cells drives transcription of a eukaryotic secretion signal peptide coding region, which is translationally joined to the coding region for the multi-functional hematopoietic receptor agonist.
  • plasmids such as pcDNA I/Neo, pRc/RSV, and pRc/CMV (obtained from Invitrogen Corp., San Diego, Calif.) can be used.
  • the eukaryotic secretion signal peptide coding region can be from the gene itself or it can be from another secreted mammalian protein (Bayne, M. L. et al., Proc. Natl. Acad. Sci. USA 84: 2638-2642, 1987).
  • the vector DNA is transfected into mammalian cells.
  • Such cells can be, for example, the COS7, HeLa, BHK, CHO, or mouse L lines.
  • the cells can be cultured, for example, in DMEM media (JRH Scientific).
  • the polypeptide secreted into the media can be recovered by standard biochemical approaches following transient expression for 24-72 hours after transfection of the cells or after establishment of stable cell lines following selection for antibiotic resistance.
  • suitable mammalian host cells and methods for transformation, culture, amplification, screening and product production and purification are known in the art. See, e.g., Gething and Sambrook, Nature, 293: 620-625, 1981), or alternatively, Kaufman et al, Mol. Cell. Biol., 5 (7): 1750-1759, 1985) or Howley et al., U.S. Pat. No. 4,419,446.
  • Another suitable mammalian cell line is the monkey COS-1 cell line.
  • a similarly useful mammalian cell line is the CV-1 cell line.
  • insect cells may be utilized as host cells in the method of the present invention. See, e.g., Miller et al., Genetic Engineering, 8: 277-298 (Plenum Press 1986) and references cited therein.
  • general methods for expression of foreign genes in insect cells using Baculovirus vectors are described in: Summers, M. D. and Smith, G. E., 1987)--A manual of methods for Baculovirus vectors and insect cell culture procedures, Texas Agricultural Experiment Station Bulletin No. 1555.
  • An expression vector is constructed comprising a Baculovirus transfer vector, in which a strong Baculovirus promoter (such as the polyhedron promoter) drives transcription of a eukaryotic secretion signal peptide coding region, which is translationally joined to the coding region for the multi-functional hematopoietic receptor agonist polypeptide.
  • a strong Baculovirus promoter such as the polyhedron promoter
  • the plasmid pVL1392 obtained from Invitrogen Corp., San Diego, Calif.
  • the multi-functional hematopoietic receptor agonists of the present invention may be useful in the treatment of diseases characterized by decreased levels of either myeloid, erythroid, lymphoid, or megakaryocyte cells of the hematopoietic system or combinations thereof. In addition, they may be used to activate mature myeloid and/or lymphoid cells.
  • diseases susceptible to treatment with the polypeptides of the present invention is leukopenia, a reduction in the number of circulating leukocytes (white cells) in the peripheral blood. Leukopenia may be induced by exposure to certain viruses or to radiation.
  • the multi-functional hematopoietic receptor agonists of the present invention may be useful in the treatment of neutropenia and, for example, in the treatment of such conditions as aplastic anemia, cyclic neutropenia, idiopathic neutropenia, Chediak-Higashi syndrome, systemic lupus erythematosus (SLE), leukemia, myelodysplastic syndrome and myelofibrosis.
  • the multi-functional hematopoietic receptor agonist of the present invention may be useful in the treatment or prevention of thrombocytopenia.
  • thrombocytopenia Currently the only therapy for thrombocytopenia is platelet transfusion which are costly and carry the significant risks of infection (HIV, HBV) and alloimmunization.
  • the multi-functional hematopoietic receptor agonist may alleviate or diminish the need for platelet transfusion. Severe thrombocytopenia may result from genetic defects such as Fanconi's Anemia, Wiscott-Aldrich, or May Hegglin syndromes. Acquired.
  • thrombocytopenia may result from auto- or allo-antibodies as in Immune Thrombocytopenia Purpura, Systemic Lupus Erythromatosis, hemolytic anemia, or fetal maternal incompatibility.
  • splenomegaly, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, infection or prosthetic heart valves may result in thrombocytopenia.
  • Severe thrombocytopenia may also result from chemotherapy and/or radiation therapy or cancer.
  • Thrombocytopenia may also result from marrow invasion by carcinoma, lymphoma, leukemia or fibrosis.
  • the multi-functional hematopoietic receptor agonists of the present invention may be useful in the mobilization of hematopoietic progenitors and stem cells in peripheral blood.
  • Peripheral blood derived progenitors have been shown to be effective in reconstituting patients in the setting of autologous marrow transplantation.
  • Hematopoietic growth factors including G-CSF and GM-CSF have been shown to enhance the number of circulating progenitors and stem cells in the peripheral blood. This has simplified the procedure for peripheral stem cell collection and dramatically decreased the cost of the procedure by decreasing the number of pheresis required.
  • the multi-functional hematopoietic receptor agonist may be useful in mobilization of stem cells and further enhance the efficacy of peripheral stem cell transplantation.
  • the multi-functional hematopoietic receptor agonists of the present invention may also be useful in the ex vivo expansion of hematopoietic progenitors and stem cells.
  • Colony stimulating factors such as hIL-3
  • hIL-3 have been administered alone, co-administered with other CSFs, or in combination with bone marrow transplants subsequent to high dose chemotherapy to treat the neutropenia and thrombocytopenia which are often the result of such treatment.
  • CSFs colony stimulating factors
  • hIL-3 have been administered alone, co-administered with other CSFs, or in combination with bone marrow transplants subsequent to high dose chemotherapy to treat the neutropenia and thrombocytopenia which are often the result of such treatment.
  • the period of severe neutropenia and thrombocytopenia may not be totally eliminated.
  • the myeloid lineage which is comprised of monocytes (macrophages), granulocytes (including neutrophils) and megakaryocytes, is critical in preventing infections and bleeding which can be life-threatening.
  • Neutropenia and thrombocytopenia may also be the result of disease, genetic disorders, drugs, toxins, radiation and many therapeutic treatments such as conventional oncology therapy.
  • Bone marrow transplants have been used to treat this patient population.
  • problems are associated with the use of bone marrow to reconstitute a compromised hematopoietic system including: 1) the number of stem cells in bone marrow, spleen, or peripheral blood is limited, 2) Graft Versus Host Disease, 3) graft rejection and 4) possible contamination with tumor cells.
  • Stem cells make up a very small percentage of the nucleated cells in the bone marrow, spleen and peripheral blood. It is clear that a dose response exists such that a greater number of stem cells will enhance hematopoietic recovery. Therefore, the in vitro expansion of stem cells should enhance hematopoietic recovery and patient survival.
  • Bone marrow from an allogeneic donor has been used to provide bone marrow for transplant.
  • Graft Versus Host Disease and graft rejection limit bone marrow transplantation even in recipients with HLA-matched sibling donors.
  • An alternative to allogeneic bone marrow transplants is autologous bone marrow transplants.
  • autologous bone marrow transplants some of the patient's own marrow is harvested prior to myeloablative therapy, e.g. high dose chemotherapy, and is transplanted back into the patient afterwards.
  • Autologous transplants eliminate the risk of Graft Versus Host Disease and graft rejection.
  • stem cells can be specifically isolated, based on the presence of specific surface antigens such as CD34+ in order to decrease tumor cell contamination of the marrow graft.
  • U.S. Pat. No. 5,061,620 relates to compositions comprising human hematopoietic stem cells provided by separating the stem cells from dedicated cells.
  • U.S. Pat. No. 5,199,942 describes a method for autologous hematopoietic cell transplantation comprising: (1) obtaining hematopoietic progenitor cells from a patient; (2) ex-vivo expansion of cells with a growth factor selected from the group consisting of IL-3, flt3 ligand, c-kit ligand, GM-CSF, IL-1, GM-CSF/IL-3 fusion protein and combinations thereof; (3) administering cellular preparation to a patient.
  • a growth factor selected from the group consisting of IL-3, flt3 ligand, c-kit ligand, GM-CSF, IL-1, GM-CSF/IL-3 fusion protein and combinations thereof.
  • U.S. Pat. No. 5,240,856 relates to a cell separator that includes an apparatus for automatically controlling the cell separation process.
  • WO 91/16116 describes devices and methods for selectively isolating and separating target cells from a mixture of cells.
  • WO 91/18972 describes methods for in vitro culturing of bone marrow, by incubating suspension of bone marrow cells, using a hollow fiber bioreactor.
  • WO 92/18615 relates to a process for maintaining and expanding bone marrow cells, in a culture medium containing specific mixtures of cytokines, for use in transplants.
  • WO 93/08268 describes a method for selectively expanding stem cells, comprising the steps of (a) separating CD34+ stem cells from other cells and (b) incubating the separated cells in a selective medium, such that the stem cells are selectively expanded.
  • WO 93/18136 describes a process for in vitro support of mammalian cells derived from peripheral blood.
  • WO 93/18648 relates to a composition comprising human neutrophil precursor cells with a high content of myeloblasts and promyelocytes for treating genetic or acquired neutropenia.
  • WO 94/08039 describes a method of enrichment for human hematopoietic stem cells by selection for cells which express c-kit protein.
  • WO 94/11493 describes a stem cell population that are CD34+ and small in size, which are isolated using a counterflow elutriation method.
  • WO 94/27698 relates to a method combining immunoaffinity separation and continuous flow centrifugal separation for the selective separation of a nucleated heterogeneous cell population from a heterogeneous cell mixture.
  • WO 94/25848 describes a cell separation apparatus for collection and manipulation of target cells.
  • stem cell refers to the totipotent hematopoietic stem cells as well as early precursors and progenitor cells which can be isolated from bone marrow, spleen or peripheral blood.
  • expansion refers to the differentiation and proliferation of the cells.
  • the present invention provides a method for selective ex-vivo expansion of stem cells, comprising the steps of: (a) separating stem cells from other cells, (b) culturing said separated stem cells with a selective media which contains multi-functional hematopoietic receptor agonist protein(s) and (c) harvesting said stems cells.
  • Stem cells as well as committed progenitor cells destined to become neutrophils, erythrocytes, platelets, etc. may be distinguished from most other cells by the presence or absence of particular progenitor marker antigens, such as D34, that are present on the surface of these cells nd/or by morphological characteristics.
  • the phenotype for a highly enriched human stem cell fraction is reported as CD34+, Thy-1+ and lin-, but it is to be understood that the present invention is not limited to the expansion of this stem cell population.
  • the CD34+ enriched human stem cell fraction can be separated by a number of reported methods, including affinity columns or beads, magnetic beads or flow cytometry using antibodies directed to surface antigens such as the CD34+.
  • CD34+ progenitors are heterogeneous, and may be divided into several sub-populations characterized by the presence or absence of co-expression of different lineage associated cell surface associated molecules.
  • the most immature progenitor cells do not express any known lineage associated markers, such as HLA-DR or CD38, but they may express CD90(thy-1).
  • Other surface antigens such as CD33, CD38, CD41, CD71, HLA-DR or c-kit can also be used to selectively isolate hematopoietic progenitors.
  • the separated cells can be incubated in selected medium in a culture flask, sterile bag or in hollow fibers.
  • Various colony stimulating factors may be utilized in order to selectively expand cells.
  • Representative factors that have been utilized for ex-vivo expansion of bone marrow include, c-kit ligand, IL-3, G-CSF, GM-CSF, IL-1, IL-6, IL-11, flt-3 ligand or combinations thereof.
  • the proliferation of the stem cells can be monitored by enumerating the number of stem cells and other cells, by standard techniques (e.g. hemacytometer, CFU, LTCIC) or by flow cytometry prior and subsequent to incubation.
  • hIL-3 has been shown to be one of the most potent in expanding peripheral blood CD34+ cells (Sato et al., Blood 82: 3600-3609 [1993], Kobayashi et al., Blood 73: 1836-1841 [1989]).
  • no single factor has been shown to be as effective as the combination of multiple factors.
  • the present invention provides methods for ex vivo expansion that utilize multi-functional hematopoietic receptor agonists that are more effective than a single factor alone.
  • Another aspect of the invention provides methods of sustaining and/or expanding hematopoietic precursor cells which includes inoculating the cells into a culture vessel which contains a culture medium that has been conditioned by exposure to a stromal cell line such as HS-5 (WO 96/02662, Roecklein and Torok-Strob, Blood 85: 997-1105, 1995) that has been supplemented with a multi-functional hematopoietic receptor agonist of the present invention.
  • a stromal cell line such as HS-5 (WO 96/02662, Roecklein and Torok-Strob, Blood 85: 997-1105, 1995) that has been supplemented with a multi-functional hematopoietic receptor agonist of the present invention.
  • hematopoietic progenitor cells are good candidates for ex vivo gene transfection.
  • Hematopoietic stem cells cycle at a very low frequency which means that growth factors may be useful to promote gene transduction and thereby enhance the clinical prospects for gene therapy.
  • Viral based vectors include; 1) replication deficient recombinant retrovirus (Boris-Lawrie and Temin, Curr. Opin. Genet. Dev. 3: 102-109 [1993], Boris-Lawrie and Temin, Annal. New York Acad. Sci. 716: 59-71 [1994], Miller, Current Top. Microbiol. Immunol.
  • Non-viral based vectors include protein/DNA complexes (Cristiano et al., PNAS USA. 90: 2122-2126 [1993], Curiel et al., PNAS USA 88: 8850-8854 [1991], Curiel, Annal. New York Acad. Sci. 716: 36-58 [1994]), electroporation and liposome mediated delivery such as cationic liposomes (Farhood et al., Annal. New York Acad. Sci. 716: 23-35 [1994]).
  • the present invention provides an improvement to the existing methods of expanding hematopoietic cells, which new genetic material has been introduced, in that it provides methods utilizing multi-functional hematopoietic receptor agonist proteins that have improved biological activity, including an activity not seen by any single colony stimulation factor.
  • drugs may cause bone marrow suppression or hematopoietic deficiencies.
  • examples of such drugs are AZT, DDI, alkylating agents and anti-metabolites used in chemotherapy, antibiotics such as chloramphenicol, penicillin, gancyclovir, daunomycin and sulfa drugs, phenothiazones, tranquilizers such as meprobamate, analgesics such as aminopyrine and dipyrone, anti-convulsants such as phenytoin or carbamazepine, antithyroids such as propylthiouracil and methimazole and diuretics.
  • the multi-functional hematopoietic receptor agonists of the present invention may be useful in preventing or treating the bone marrow suppression or hematopoietic deficiencies which often occur in patients treated with these drugs.
  • Hematopoietic deficiencies may also occur as a result of viral, microbial or parasitic infections and as a result of treatment for renal disease or renal failure, e.g., dialysis.
  • the multi-functional hematopoietic receptor agonists of the present invention may be useful in treating such hematopoietic deficiencies.
  • the treatment of hematopoietic deficiency may include administration of a pharmaceutical composition containing the multi-functional hematopoietic receptor agonists to a patient.
  • the multi-functional hematopoietic receptor agonists of the present invention may also be useful for the activation and amplification of hematopoietic precursor cells by treating these cells in vitro with the multi-functional hematopoietic receptor agonist proteins of the present invention prior to injecting the cells into a patient.
  • Immunodeficiencies may also be beneficially affected by treatment with the multi-functional hematopoietic receptor agonists of the present invention.
  • Immunodeficiencies may be the result of viral infections, e.g., HTLVI, HTLVII, HTLVIII, severe exposure to radiation, cancer therapy or the result of other medical treatment.
  • the multi-functional hematopoietic receptor agonists of the present invention may also be employed, alone or in combination with other colony stimulating factors, in the treatment of other blood cell deficiencies, including thrombocytopenia (platelet deficiency), or anemia.
  • Other uses for these novel polypeptides are the in vivo and ex vivo treatment of patients recovering from bone marrow transplants, and in the development of monoclonal and polyclonal antibodies generated by standard methods for diagnostic or therapeutic use.
  • compositions for treating the conditions referred to above.
  • Such compositions comprise a therapeutically effective amount of one or more of the multi-functional hematopoietic receptor agonists of the present invention in a mixture with a pharmaceutically acceptable carrier.
  • This composition can be administered either parenterally, intravenously or subcutaneously.
  • the therapeutic composition for use in this invention is preferably in the form of a pyrogen-free, parenterally acceptable aqueous solution.
  • the preparation of such a parenterally acceptable protein solution having due regard to pH, isotonicity, stability and the like, is within the skill of the art.
  • a daily regimen may be in the range of 0.2-150 ⁇ g/kg of multi-functional hematopoietic receptor agonist protein per kilogram of body weight. Dosages would be adjusted relative to the activity of a given multi-functional hematopoietic receptor agonist protein and it would not be unreasonable to note that dosage regimens may include doses as low as 0.1 microgram and as high as 1 milligram per kilogram of body weight per day.
  • multi-functional hematopoietic receptor agonist would be adjusted higher or lower than the range of 0.2-150 micrograms per kilogram of body weight.
  • these include co-administration with other colony stimulating factors or IL-3 variants or growth factors; co-administration with chemotherapeutic drugs and/or radiation; the use of glycosylated multi-functional hematopoietic receptor agonist protein; and various patient-related issues mentioned earlier in this section.
  • the therapeutic method and compositions may also include co-administration with other human factors.
  • CSFs colony stimulating factors
  • cytokines cytokines
  • lymphokines hematopoietic growth factors and interleukins
  • GM-CSF colony stimulating factor
  • G-CSF G-CSF
  • c-mpl ligand also known as TPO or MGDF
  • M-CSF erythropoietin
  • EPO erythropoietin
  • IL-1 IL-4, IL-2, IL-3, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-15, IL-16, LIF, flt3 ligand, and eosinophil differentiation factor, stem cell factor (SCF) also known as steel factor or c-kit ligand, or combinations thereof.
  • SCF stem cell factor
  • the dosage recited above would be adjusted to compensate for such additional components in the therapeutic composition. Progress of the treated patient can be monitored by periodic assessment of the
  • E. coli strains such as DH5 ⁇ TM (Life Technologies, Gaithersburg, Md.) and TG1 (Amersham Corp., Arlington Heights, Ill.) are used for transformation of ligation reactions and are the source of plasmid DNA for transfecting mammalian cells.
  • E. coli strains such as JM101 (Yanisch-Perron, et al., Gene, 33: 103-119, 1985) and MON105 (Obukowicz, et al., Appl. and Envir. Micr., 58: 1511-1523, 1992) can be used for expressing the multi-functional hematopoietic receptor agonist of the present invention in the cytoplasm or periplasmic space.
  • MON105 ATCC#55204 F-, lambda-,IN(rrnD, rrE)1, rpoD+, rpoH358
  • DH5 ⁇ TM F-, phi80dlacZdeltaM15, delta(lacZYA-argF)U169, deoR, recA1, endA1, hsdR17(rk-,mk+), phoA, supE44lamda-, thi-1, gyrA96, relA1
  • TG1 delta(lac-pro), supE, thi-1, hsdD5/F'(traD36, proA+B+,
  • JM101 ATCC#33876 delta (pro lac), supE, thi, F'(traD36, proA+B+, lacIq, lacZdeltaM15)
  • DH5 ⁇ TM Subcloning efficiency cells are purchased as competent cells and are ready for transformation using the manufacturer's protocol, while both E. coli strains TG1 and MON105 are rendered competent to take up DNA using a CaCl 2 method.
  • 20 to 50 mL of cells are grown in LB medium (1% bacto-tryptone, 0.5% bacto-yeast extract, 150 mM NaCl) to a density of approximately 1.0 optical density unit at 600 nanometers (OD600) as measured by a Baush & Lomb Spectronic spectrophotometer (Rochester, N.Y.).
  • the cells are collected by centrifugation and resuspended in one-fifth culture volume of CaCl 2 solution (50 mM CaCl 2 , 10 mM Tris-Cl, pH7.4) and are held at 4° C. for 30 minutes.
  • the cells are again collected by centrifugation and resuspended in one-tenth culture volume of CaCl 2 solution.
  • Ligated DNA is added to 0.2 mL of these cells, and the samples are held at 4° C. for 30-60 minutes.
  • the samples are shifted to 42° C. for two minutes and 1.0 mL of LB is added prior to shaking the samples at 37° C. for one hour.
  • Cells from these samples are spread on plates (LB medium plus 1.5% bacto-agar) containing either ampicillin (100 micrograms/mL, ug/mL) when selecting for ampicillin-resistant transformants, or spectinomycin (75 ug/mL) when selecting for spectinomycin-resistant transformants.
  • ampicillin 100 micrograms/mL, ug/mL
  • spectinomycin 75 ug/mL
  • Method I Creation of genes with new N-terminus/C-terminus which contain a linker region (L 2 ).
  • the first primer set (“new start” and “linker start”) is used to create and amplify, from the original gene sequence, the DNA fragment (“Fragment Start”) that contains the sequence encoding the new N-terminal portion of the new protein followed by the linker (L 2 ) that connects the C-terminal and N-terminal ends of the original protein.
  • the second primer set (“new stop” and “linker stop”) is used to create and amplify, from the original gene sequence, the DNA fragment (“Fragment Stop”) that encodes the same linker as used above, followed by the new C-terminal portion of the new protein.
  • the "new start” and “new stop” primers are designed to include the appropriate restriction sites which allow cloning of the new gene into expression plasmids.
  • Typical PCR conditions are one cycle 95° C. melting for two minutes; 25 cycles 94° C. denaturation for one minute, 50° C. annealing for one minute and 72° C. extension for one minute; plus one cycle 72° C. extension for seven minutes.
  • a Perkin Elmer GeneAmp PCR Core Reagents kit is used.
  • a 100 ul reaction contains 100 pmole of each primer and one ug of template DNA; and 1 ⁇ PCR buffer, 200 uM dGTP, 200 uM DATP, 200 uM dTTP, 200 uM dCTP, 2.5 units AmpliTaq DNA polymerase and 2 mM MgCl2.
  • PCR reactions are performed in a Model 480 DNA thermal cycler (Perkin Elmer Corporation, Norwalk, Conn.).
  • primers "new start” and “new stop” are added to the annealed fragments to create and amplify the full-length new N-terminus/C-terminus gene.
  • Typical PCR conditions are one cycle 95° C. melting for two minutes; 25 cycles 94° C. denaturation for one minute, 60° C. annealing for one minute and 72° C. extension for one minute; plus one cycle 72° C. extension for seven minutes.
  • a Perkin Elmer GeneAmp PCR Core Reagents kit is used.
  • a 100 ul reaction contains 100 pmole of each primer and approximately 0.5 ug of DNA; and 1 ⁇ PCR buffer, 200 uM dGTP, 200 uM dATP, 200 uM dTTP, 200 uM dCTP, 2.5 units AmpliTaq DNA polymerase and 2 mM MgCl2.
  • PCR reactions are purified using a Wizard PCR Preps kit (Promega).
  • New N-terminus/C-terminus genes without a linker joining the original N-terminus and C-terminus can be made using two steps of PCR amplification and a blunt end ligation. The steps are illustrated in FIG. 3.
  • the primer set (“new start” and "P-bl start”) is used to create and amplify, from the original gene sequence, the DNA fragment (“Fragment Start”) that contains the sequence encoding the new N-terminal portion of the new protein.
  • the primer set (“new stop” and "P-bl stop”) is used to create and amplify, from gene sequence, the DNA fragment (“Fragment Stop”) that contains the sequence encoding the new C-terminal portion of the new protein.
  • the “new start” and “new stop” primers are designed to include appropriate restriction sites which allow cloning of the new gene into expression vectors. Typical PCR conditions are one cycle 95° C. melting for two minutes; 25 cycles 94° C. denaturation for one minute, 50° C. annealing for 45 seconds and 72° C. extension for 45 seconds. Deep Vent polymerase (New England Biolabs) is used to reduce the occurrence of overhangs in conditions recommended by the manufacturer.
  • the "P-bl start” and “P-bl stop” primers are phosphorylated at the 5' end to aid in the subsequent blunt end ligation of "Fragment Start” and “Fragment Stop” to each other.
  • a 100 ul reaction contained 150 pmole of each primer and one ug of template DNA; and 1 ⁇ Vent buffer (New England Biolabs), 300 uM dGTP, 300 uM DATP, 300 uM dTTP, 300 uM dCTP, and 1 unit Deep Vent polymerase.
  • PCR reactions are performed in a Model 480 DNA thermal cycler (Perkin Elmer Corporation, Norwalk, Conn.). PCR reaction products are purified using a Wizard PCR Preps kit (Promega).
  • the primers are designed to include appropriate restriction sites which allow for the cloning of the new gene into expression vectors.
  • "Fragment Start” is designed to create NcoI restriction site
  • “Fragment Stop” is designed to create a HindIII restriction site.
  • Restriction digest reactions are purified using a Magic DNA Clean-up System kit (Promega). Fragments Start and Stop are resolved on a 1% TAE gel, stained with ethidium bromide and isolated using a Qiaex Gel Extraction kit (Qiagen). These fragments are combined with and annealed to the ends of the ⁇ 3800 base pair NcoI/HindIII vector fragment of pMON3934 by heating at 50° C. for ten minutes and allowed to slow cool.
  • the three fragments are ligated together using T4 DNA ligase (Boehringer Mannheim).
  • T4 DNA ligase Boehringer Mannheim
  • the result is a plasmid containing the full-length new N-terminus/C-terminus gene.
  • a portion of the ligation reaction is used to transform E. coli strain DH5a cells (Life Technologies, Gaithersburg, Md.). Plasmid DNA is purified and sequence confirmed as below.
  • New N-terminus/C-terminus genes can be made based on the method described in R. A. Horlick, et al Protein Eng. 5: 427-431, 1992). Polymerase chain reaction (PCR) amplification of the new N-terminus/C-terminus genes is performed using a tandemly duplicated template DNA. The steps are illustrated in FIG. 3.
  • PCR Polymerase chain reaction
  • the tandemly-duplicated template DNA is created by cloning and contains two copies of the gene separated by DNA sequence encoding a linker connecting the original C- and N-terminal ends of the two copies of the gene.
  • Specific primer sets are used to create and amplify a full-length new N terminus/C-terminus gene from the tandemly-duplicated template DNA. These primers are designed to include appropriate restriction sites which allow for the cloning of the new gene into expression vectors.
  • Typical PCR conditions are one cycle 95° C. melting for two minutes; 25 cycles 94° C. denaturation for one minute, 50° C. annealing for one minute and 72° C. extension for one minute; plus one cycle 72° C. extension for seven minutes.
  • a Perkin Elmer GeneAmp PCR Core Reagents kit (Perkin Elmer Corporation, Norwalk, Conn.) is used.
  • a 100 ul reaction contains 100 pmole of each primer and one ug of template DNA; and 1 ⁇ PCR buffer, 200 uM dGTP, 200 uM DATP, 200 uM dTTP, 200 uM dCTP, 2.5 units AmpliTaq DNA polymerase and 2 mM MgCl 2 .
  • PCR reactions are performed in a Model 480 DNA thermal cycler (Perkin Elmer Corporation, Norwalk, Conn.). PCR reactions are purified using a Wizard PCR Preps kit (Promega).
  • the new N-terminus/C-terminus gene is digested with restriction endonucleases to create ends that are compatible to insertion into an expression vector containing another colony stimulating factor gene.
  • This expression vector is likewise digested with restriction endonucleases to form compatible ends.
  • the gene and the vector DNAs are combined and ligated using T4 DNA ligase. A portion of the ligation reaction is used to transform E. coli. Plasmid DNA is purified and sequenced to confirm the correct insert. The correct clones are grown for protein expression.
  • Plasmid DNA can be isolated by a number of different methods and using commercially available kits known to those skilled in the art. A few such methods are shown herein. Plasmid DNA is isolated using the Promega WizardTM Miniprep kit (Madison, Wis.), the Qiagen QIAwell Plasmid isolation kits (Chatsworth, Calif.) or Qiagen Plasmid Midi kit. These kits follow the same general procedure for plasmid DNA isolation. Briefly, cells are pelleted by centrifugation (5000 ⁇ g), plasmid DNA released with sequential NaOH/acid treatment, and cellular debris is removed by centrifugation (10000 ⁇ g).
  • the supernatant (containing the plasmid DNA) is loaded onto a column containing a DNA-binding resin, the column is washed, and plasmid DNA eluted with TE. After screening for the colonies with the plasmid of interest, the E. coli cells are inoculated into 50-100 mls of LB plus appropriate antibiotic for overnight growth at 37° C. in an air incubator while shaking.
  • the purified plasmid DNA is used for DNA sequencing, further restriction enzyme digestion, additional subcloning of DNA fragments and transfection into mammalian, E. coli or other cells.
  • Purified plasmid DNA is resuspended in dH 2 O and quantitated by measuring the absorbance at 260/280 nm in a Bausch and Lomb Spectronic 601 UV spectrometer.
  • DNA samples are sequenced using ABI PRISMTM DyeDeoxyTM terminator sequencing chemistry (Applied Biosystems Division of Perkin Elmer Corporation, Lincoln City, Calif.) kits (Part Number 401388 or 402078) according to the manufacturers suggested protocol usually modified by the addition of 5% DMSO to the sequencing mixture. Sequencing reactions are performed in a Model 480 DNA thermal cycler (Perkin Elmer Corporation, Norwalk, Conn.) following the recommended amplification conditions.
  • Samples are purified to remove excess dye terminators with Centri-SepTM spin columns (Princeton Separations, Adelphia, N.J.) and lyophilized. Fluorescent dye labeled sequencing reactions are resuspended in deionized formamide, and sequenced on denaturing 4.75% polyacrylamide-8M urea gels using an ABI Model 373A automated DNA sequencer. Overlapping DNA sequence fragments are analyzed and assembled into master DNA contigs using Sequencher v2.1 DNA analysis software (Gene Codes Corporation, Ann Arbor, Mich.).
  • the BHK-21 cell line can be obtained from the ATCC (Rockville, Md.). The cells are cultured in Dulbecco's modified Eagle media (DMEM/high-glucose), supplemented to 2 mM (mM) L-glutamine and 10% fetal bovine serum (FBS). This formulation is designated BHK growth media. Selective media is BHK growth media supplemented with 453 units/mL hygromycin B (Calbiochem, San Diego, Calif.).
  • DMEM/high-glucose Dulbecco's modified Eagle media
  • FBS fetal bovine serum
  • the BHK-21 cell line was previously stably transfected with the HSV transactivating protein VP16, which transactivates the IE110 promoter found on the plasmid pMON3359 (See Hippenmeyer et al., Bio/Technology, pp.1037-1041, 1993).
  • the VP16 protein drives expression of genes inserted behind the IE110 promoter.
  • BHK-21 cells expressing the transactivating protein VP16 are designated BHK-VP16.
  • the plasmid pMON1118 See Highkin et al., Poultry Sci., 70: 970-981, 1991 expresses the hygromycin resistance gene from the SV40 promoter.
  • a similar plasmid is available from ATCC, pSV2-hph.
  • BHK-VP16 cells are seeded into a 60 millimeter (mm) tissue culture dish at 3 ⁇ 10 5 cells per dish 24 hours prior to transfection.
  • Cells are transfected for 16 hours in 3 mL of "OPTIMEM”TM (Gibco-BRL, Gaithersburg, Md.) containing 10 ug of plasmid DNA containing the gene of interest, 3 ug hygromycin resistance plasmid, pMON1118, and 80 ug of Gibco-BRL "LIPOFECTAMINE”TM per dish.
  • the media is subsequently aspirated and replaced with 3 mL of growth media.
  • media from each dish is collected and assayed for activity (transient conditioned media).
  • the cells are removed from the dish by trypsin-EDTA, diluted 1:10 and transferred to 100 mm tissue culture dishes containing 10 mL of selective media. After approximately 7 days in selective media, resistant cells grow into colonies several millimeters in diameter. The colonies are removed from the dish with filter paper (cut to approximately the same size as the colonies and soaked in trypsin/EDTA) and transferred to individual wells of a 24 well plate containing 1 mL of selective media. After the clones are grown to confluence, the conditioned media is re-assayed, and positive clones are expanded into growth media.
  • E. coli strain MON105 or JM101 harboring the plasmid of interest are grown at 37° C. in M9 plus casamino acids medium with shaking in a air incubator Model G25 from New Brunswick Scientific (Edison, N.J.). Growth is monitored at OD600 until it reaches a value of 1.0 at which time Nalidixic acid (10 milligrams/mL) in 0.1 N NaOH is added to a final concentration of 50 ⁇ g/mL. The cultures are then shaken at 37° C. for three to four additional hours. A high degree of aeration is maintained throughout culture period in order to achieve maximal production of the desired gene product. The cells are examined under a light microscope for the presence of inclusion bodies (IB).
  • IB inclusion bodies
  • One mL aliquots of the culture are removed for analysis of protein content by boiling the pelleted cells, treating them with reducing buffer and electrophoresis via SDS-PAGE (see Maniatis et al. Molecular Cloning: A Laboratory Manual, 1982).
  • the culture is centrifuged (5000 ⁇ g) to pellet the cells.
  • the cell pellet from a 330 mL E. coli culture is resuspended in 15 mL of sonication buffer (10 mM 2-amino-2-(hydroxymethyl) 1,3-propanediol hydrochloride (Tris-HCl), pH 8.0+1 mM ethylenediaminetetraacetic acid (EDTA).
  • sonication buffer 10 mM 2-amino-2-(hydroxymethyl) 1,3-propanediol hydrochloride (Tris-HCl), pH 8.0+1 mM ethylenediaminetetraacetic acid (EDTA).
  • Tris-HCl 2-amino-2-(hydroxymethyl) 1,3-propanediol hydrochloride
  • EDTA ethylenediaminetetraacetic acid
  • These resuspended cells are sonicated using the microtip probe of a Sonicator Cell Disruptor (Model W-375, Heat Systems-Ultrasonics, Inc., Farmingdale,
  • the IB pellet is resuspended in 10 mL of 50 mM Tris-HCl, pH 9.5, 8 M urea and 5 mM dithiothreitol (DTT) and stirred at room temperature for approximately 45 minutes to allow for denaturation of the expressed protein.
  • DTT dithiothreitol
  • the extraction solution is transferred to a beaker containing 70 mL of 5 mM Tris-HCl, pH 9.5 and 2.3 M urea and gently stirred while exposed to air at 4° C. for 18 to 48 hours to allow the proteins to refold.
  • Refolding is monitored by analysis on a Vydac (Hesperia, Calif.) C18 reversed phase high pressure liquid chromatography (RP-HPLC) column (0.46 ⁇ 25 cm).
  • RP-HPLC reversed phase high pressure liquid chromatography
  • a linear gradient of 40% to 65% acetonitrile, containing 0.1% trifluoroacetic acid (TFA) is employed to monitor the refold. This gradient is developed over 30 minutes at a flow rate of 1.5 mL per minute.
  • Denatured proteins generally elute later in the gradient than the refolded proteins.
  • contaminating E. coli proteins are removed by acid precipitation.
  • the pH of the refold solution is titrated to between pH 5.0 and pH 5.2 using 15% (v/v) acetic acid (HOAc). This solution is stirred at 4° C. for 2 hours and then centrifuged for 20 minutes at 12,000 ⁇ g to pellet any insoluble protein.
  • the supernatant from the acid precipitation step is dialyzed using a Spectra/Por 3 membrane with a molecular weight cut off (MWCO) of 3,500 daltons.
  • the dialysis is against 2 changes of 4 liters (a 50-fold excess) of 10 mM Tris-HCl, pH 8.0 for a total of 18 hours. Dialysis lowers the sample conductivity and removes urea prior to DEAE chromatography.
  • the sample is then centrifuged (20 minutes at 12,000 ⁇ g) to pellet any insoluble protein following dialysis.
  • a Bio-Rad Bio-Scale DEAE2 column (7 ⁇ 52 mm) is used for ion exchange chromatography.
  • the column is equilibrated in a buffer containing 10 mM Tris-HCl, pH 8.0, and a 0-to-500 mM sodium chloride (NaCl) gradient, in equilibration buffer, over 45 column volumes is used to elute the protein.
  • a flow rate of 1.0 mL per minute is used throughout the run.
  • Column fractions (2.0 mL per fraction) are collected across the gradient and analyzed by RP HPLC on a Vydac (Hesperia, Calif.) C18 column (0.46 ⁇ 25 cm).
  • TFA trifluoroacetic acid
  • the folded proteins can be affinity purified using affinity reagents such as mAbs or receptor subunits attached to a suitable matrix.
  • affinity reagents such as mAbs or receptor subunits attached to a suitable matrix.
  • purification can be accomplished using any of a variety of chromatographic methods such as: ion exchange, gel filtration or hydrophobic chromatography or reversed phase HPLC.
  • the purified protein is analyzed by RP-HPLC, electrospray mass spectrometry, and SDS-PAGE.
  • the protein quantitation is done by amino acid composition, RP-HPLC, and Bradford protein determination. In some cases tryptic peptide mapping is performed in conjunction with electrospray mass spectrometry to confirm the identity of the protein.
  • the factor-dependent cell line AML 193 was obtained from the American Type Culture Collection (ATCC, Rockville, Md.). This cell line, established from a patient with acute myelogenous leukemia, is a growth factor dependent cell line which displayed enhanced growth in GM-CSF supplemented medium (Lange, B., et al., Blood 70: 192, 1987; Valtieri, M., et al., J. Immunol. 138: 4042, 1987). The ability of AML 193 cells to proliferate in the presence of human IL-3 has also been documented. (Santoli, D., et al., J. Immunol. 139: 348, 1987).
  • a cell line variant was used, AML 193 1.3, which was adapted for long term growth in IL-3 by washing out the growth factors and starving the cytokine dependent AML 193 cells for growth factors for 24 hours. The cells are then replated at 1 ⁇ 10 5 cells/well in a 24 well plate in media containing 100 U/mL IL-3. It took approximately 2 months for the cells to grow rapidly in IL-3. These cells are maintained as AML 193 1.3 thereafter by supplementing tissue culture medium (see below) with human IL-3.
  • AML 193 1.3 cells are washed 6 times in cold Hanks balanced salt solution (HBSS, Gibco, Grand Island, N.Y.) by centrifuging cell suspensions at 250 ⁇ g for 10 minutes followed by decantation of the supernatant. Pelleted cells are resuspended in HBSS and the procedure is repeated until six wash cycles are completed. Cells washed six times by this procedure are resuspended in tissue culture medium at a density ranging from 2 ⁇ 10 5 to 5 ⁇ 10 5 viable cells/mL. This medium is prepared by supplementing Iscove's modified Dulbecco's Medium (IMDM, Hazelton, Lenexa, Kans.) with albumin, transferrin, lipids and 2-mercaptoethanol.
  • IMDM Iscove's modified Dulbecco's Medium
  • Bovine albumin (Boehringer-Mannheim, Indianapolis, Ind.) is added at 500 ⁇ g/mL; human transferrin (Boehringer-Mannheim, Indianapolis, Ind.) is added at 100 ⁇ g/mL; soybean lipid (Boehringer-Mannheim, Indianapolis, Ind.) is added at 50 ⁇ g/mL; and 2-mercaptoethanol (Sigma, St. Louis, Mo.) is added at 5 ⁇ 10 -5 M.
  • Serial dilutions of human interleukin-3 or multi-functional hematopoietic receptor agonist proteins are made in triplicate series in tissue culture medium supplemented as stated above in 96 well Costar 3596 tissue culture plates. Each well contained 50 ⁇ l of medium containing interleukin-3 or multi-functional hematopoietic receptor agonist proteins once serial dilutions are completed. Control wells contained tissue culture medium alone (negative control). AML 193 1.3 cell suspensions prepared as above are added to each well by pipetting 50 ⁇ l (2.5 ⁇ 10 4 cells) into each well. Tissue culture plates are incubated at 37° C. with 5% CO 2 in humidified air for 3 days.
  • 0.5 ⁇ Ci 3 H-thymidine (2 Ci/mM, New England Nuclear, Boston, Mass.) is added in 50 ⁇ l of tissue culture medium. Cultures are incubated at 37° C. with 5% CO 2 in humidified air for 18-24 hours. Cellular DNA is harvested onto glass filter mats (Pharmacia LKB, Gaithersburg, Md.) using a TOMTEC cell harvester (TOMTEC, Orange, Conn.) which utilized a water wash cycle followed by a 70% ethanol wash cycle. Filter mats are allowed to air dry and then placed into sample bags to which scintillation fluid (Scintiverse II, Fisher Scientific, St. Louis, Mo.
  • TOMTEC TOMTEC, Orange, Conn.
  • BetaPlate Scintillation Fluid Pharmacia LKB, Gaithersburg, Md.
  • Beta emissions of samples from individual tissue culture wells are counted in a LKB BetaPlate model 1205 scintillation counter (Pharmacia LKB, Gaithersburg, Md.) and data is expressed as counts per minute of 3 H-thymidine incorporated into cells from each tissue culture well.
  • Activity of each human interleukin-3 preparation or multi-functional hematopoietic receptor agonist protein preparation is quantitated by measuring cell proliferation ( 3 H-thymidine incorporation) induced by graded concentrations of interleukin-3 or multi-functional hematopoietic receptor agonist.
  • concentration ranges from 0.05 pM-10 5 pM are quantitated in these assays.
  • the multi-functional hematopoietic receptor agonist proteins were tested in a concentration range of 2000 pM to 0.06 pM titrated in serial 2 fold dilutions.
  • the proliferation assay was performed with the multi-functional hematopoietic receptor agonist plus and minus neutralizing monoclonal antibodies to the hIL-3 receptor agonist portion.
  • a fusion molecule with the factor Xa cleavage site was cleaved then purified and the halves of the molecule were assayed for proliferative activity.
  • the c-mpl ligand proliferative activity can be assayed using a subclone of the pluripotential human cell line TF1 (Kitamura et al., J. Cell Physiol 140: 323-334. [1989]). TF1 cells are maintained in h-IL3 (100 U/mL). To establish a sub-clone responsive to c-mpl ligand, cells are maintained in passage media containing 10% supernatant from BHK cells transfected with the gene expressing the 1-153 form of c-mpl ligand (pMON26448). Most of the cells die, but a subset of cells survive.
  • a c-mpl ligand responsive clone is selected, and these cells are split into passage media to a density of 0.3 ⁇ 10 6 cells/mL the day prior to assay set-up.
  • Passage media for these cells is the following: RPMI 1640 (Gibco), 10% FBS (Harlan, Lot #91206), 10% c-mpl ligand supernatant from transfected BHK cells, 1 mM sodium pyruvate (Gibco), 2 mM glutamine (Gibco), and 100 ug/mL penicillin-streptomycin (Gibco).
  • ATL medium consists of the following: IMDM (Gibco), 500 ug/mL of bovine serum albumin, 100 ug/mL of human transferrin, 50 ug/mL soybean lipids, 4 ⁇ 10-8M beta-mercaptoethanol and 2 mL of A9909 (Sigma, antibiotic solution) per 1000 mL of ATL.
  • Cells are diluted in assay media to a final density of 0.25 ⁇ 10 6 cells/mL in a 96-well low evaporation plate (Costar) to a final volume of 50 ul.
  • Transient supernatants (conditioned media) from transfected clones are added at a volume of 50 ul as duplicate samples at a final concentration of 50% and diluted three-fold to a final dilution of 1.8%.
  • Triplicate samples of a dose curve of IL-3 variant pMON13288 starting at 1 ng/mL and diluted using three-fold dilutions to 0.0014 ng/mL is included as a positive control. Plates are incubated at 5% CO 2 and 37° C. At day six of culture, the plate is pulsed with 0.5 Ci of 3H/well (NEN) in a volume of 20 ul/well and allowed to incubate at 5% CO 2 and 37° C. for four hours. The plate is harvested and counted on a Betaplate counter.
  • in vitro cell based assays known to those skilled in the art, may also be useful to determine the activity of the multi-functional hematopoietic receptor agonists depending on the factors that comprise the molecule in a similar manner as described in the AML 193.1.3 cell proliferation assay. The following are examples of other useful assays.
  • TF1 proliferation assay TF1 is a pluripotential human cell line (Kitamura et al., J. Cell Physiol 140: 323-334. [1989]) that responds to hIL-3.
  • 32D proliferation assay 32D is a murine IL-3 dependent cell line which does not respond to human IL-3 but does respond to human G-CSF which is not species restricted.
  • Baf/3 proliferation assay Baf/3 is a murine IL-3 dependent cell line which does not respond to human IL-3 or human c-mpl ligand but does respond to human G-CSF which is not species restricted.
  • T1165 proliferation assay T1165 cells are a IL-6 dependent murine cell line (Nordan et al., 1986) which respond to IL-6 and IL-11.
  • Human Plasma Clot meg-CSF Assay Used to assay megakaryocyte colony formation activity (Mazur et al., 1981).
  • Cell lines such as the murine Baf/3 cell line can be transfected with a colony stimulating factor receptor, such as the human G-CSF receptor or human c-mpl receptor, which the cell line does not have. These transfected cell lines can be used to determine the activity of the ligand for which the receptor has been transfected into the cell line.
  • a colony stimulating factor receptor such as the human G-CSF receptor or human c-mpl receptor
  • Baf/3 cell line was made by cloning the cDNA encoding c-mpl from a library made from a c-mpl responsive cell line and cloned into the multiple cloning site of the plasmid pcDNA3 (Invitrogen, San Diego Calif.). Baf/3 cells were transfected with the plasmid via electroporation. The cells were grown under G418 selection in the presence of mouse IL-3 in Wehi conditioned media. Clones were established through limited dilution.
  • the human G-CSF receptor can be transfected into the Baf/3 cell line and used to determine the bioactivity of the multi-functional hematopoietic receptor agoinsts.
  • Bone marrow aspirates (15-20 mL) were obtained from normal allogeneic marrow donors after informed consent.
  • Cells were diluted 1:3 in phosphate buffered saline (PBS, Gibco-BRL), 30 mL were layered over 15 mL Histopaque-1077 (Sigma) and centrifuged for 30 minutes at 300 RCF. The mononuclear interface layer was collected and washed in PBS.
  • CD34+ cells were enriched from the mononuclear cell preparation using an affinity column per manufacturers instructions (CellPro, Inc, Bothell Wash.).
  • CD34+ cells After enrichment, the purity of CD34+ cells was 70% on average as determined by using flow cytometric analysis using anti-CD34 monoclonal antibody conjugated to fluorescein and anti-CD38 conjugated to phycoerythrin (Becton Dickinson, San Jose Calif.).
  • MK buffer 13.6 mM sodium citrate, 1 mM theophylline, 2.2 ⁇ m PGE1, 11 mM glucose, 3% w/v BSA, in PBS, pH 7.4,
  • MK buffer 13.6 mM sodium citrate, 1 mM theophylline, 2.2 ⁇ m PGE1, 11 mM glucose, 3% w/v BSA, in PBS, pH 7.4,
  • CD41a-FITC Green fluorescence
  • PI red fluorescence
  • CD34+ enriched population were isolated as described above.
  • Cells were suspended at 25,000 cells/mL with or without cytokine(s) in a media consisting of a base Iscoves IMDM media supplemented with 0.3% BSA, 0.4 mg/mL apo-transferrin, 6.67 ⁇ M FeCl 2 , 25 ⁇ g/mL CaCl 2 , 25 ⁇ g/mL L-asparagine, 500 ⁇ g/mL ⁇ -amino-n-caproic acid and penicillin/streptomycin.
  • thrombin Prior to plating into 35 mm plates, thrombin was added (0.25 Units/mL) to initiate clot formation.
  • Cells were incubated at 37° C. for 13 days at 5% CO 2 in a 37° C. humidified incubator.
  • This assay reflects the ability of colony stimulating factors to stimulate normal bone marrow cells to produce different types of hematopoietic colonies in vitro (Bradley et al., Aust. Exp Biol. Sci. 44: 287-300, 1966), Pluznik et al., J. Cell Comp. Physio 66: 319-324, 1965).
  • CD34+ cells are counted and CD34+ cells are selected using the Ceprate LC (CD34) Kit (CellPro Co., Bothel, Wash.) column. This fractionation is performed since all stem and progenitor cells within the bone marrow display CD34 surface antigen.
  • Cultures are set up in triplicate with a final volume of 1.0 mL in a 35 ⁇ 10 mm petri dish (Nunc#174926).
  • Culture medium is purchased from Terry Fox Labs. (HCC-4230 medium (Terry Fox Labs, Vancouver, B.C., Canada) and erythropoietin (Amgen, Thousand Oaks, Calif.) is added to the culture media.
  • 3,000-10,000 CD34+ cells are added per dish.
  • Recombinant IL-3 purified from mammalian cells or E. coli, and multi-functional hematopoietic receptor agonist proteins, in conditioned media from transfected mammalian cells or purified from conditioned media from transfected mammalian cells or E.
  • coli are added to give final concentrations ranging from 0.001 nM to 10 nM.
  • Recombinant hIL-3, GM-CSF, c-mpl ligand and multi-functional hematopoietic receptor agonist are supplied in house.
  • G-CSF Neurogen
  • Cultures are resuspended using a 3 cc syringe and 1.0 mL is dispensed per dish.
  • Control baseline response cultures received no colony stimulating factors.
  • Positive control cultures received conditioned media (PHA stimulated human cells: Terry Fox Lab. H2400). Cultures are incubated at 37° C., 5% CO 2 in humidified air.
  • Hematopoietic colonies which are defined as greater than 50 cells are counted on the day of peak response (days 10-11) using a Nikon inverted phase microscope with a 40 ⁇ objective combination. Groups of cells containing fewer than 50 cells are referred to as clusters. Alternatively colonies can be identified by spreading the colonies on a slide and stained or they can be picked, resuspended and spun onto cytospin slides for staining.
  • Bone marrow cells are traditionally used for in vitro assays of hematopoietic colony stimulating factor (CSF) activity.
  • CSF colony stimulating factor
  • human bone marrow is not always available, and there is considerable variability between donors.
  • Umbilical cord blood is comparable to bone marrow as a source of hematopoietic stem cells and progenitors (Broxmeyer et al., PNAS USA 89: 4109-113, 1992; Mayani et al., Blood 81: 3252-3258, 1993). In contrast to bone marrow, cord blood is more readily available on a regular basis.
  • There is also a potential to reduce assay variability by pooling cells obtained fresh from several donors, or to create a bank of cryopreserved cells for this purpose.
  • CFU-GM granulocyte/macrophage colonies
  • HPP-CFC high proliferative potential colony forming cell
  • Mononuclear cells are isolated from cord blood within 24 hr. of collection, using a standard density gradient (1.077 g/mL Histopaque).
  • Cord blood MNC have been further enriched for stem cells and progenitors by several procedures, including immunomagnetic selection for CD14-, CD34+ cells; panning for SBA-, CD34+ fraction using coated flasks from Applied Immune Science (Santa Clara, Calif.); and CD34+ selection using a CellPro (Bothell, Wash.) avidin column. Either freshly isolated or cryopreserved CD34+ cell enriched fractions are used for the assay.
  • Duplicate cultures for each serial dilution of sample are #prepared with 1 ⁇ 104 cells in 1 ml of 0.9% methycellulose containing medium without additional growth factors (Methocult H4230 from Stem Cell Technologies, Vancouver, BC.).
  • Methocult H4330 containing erythropoietin (EPO) was used instead of Methocult H4230, or Stem Cell Factor (SCF), 50 ng/mL (Biosource International, Camarillo, Calif.) was added. After culturing for 7-9 days, colonies containing >30 cells are counted. In order to rule out subjective bias in scoring, assays are scored blind.
  • a new mammalian expression vector was constructed to accept NcoI-HindIII or AflIII-HindIII gene fragments in-frame and 3' to the hIL-3 receptor agonist pMON13146 (WO 94/12638) gene and a mouse IgG2b linker fragment.
  • the single AflIII site was removed from pMON3934, which is a derivative of pMON3359.
  • pMON3359 is a pUC18-based vector containing a mammalian expression cassette.
  • the cassette includes a herpes simplex viral promoter IE110 (-800 to +120) followed by a modified human IL-3 signal peptide sequence and an SV40 late poly-adenylation (poly-A) signal which has been subcloned into the pUC18 polylinker (See Hippenmeyer et al., Bio/Technology, 1993, pp.1037-1041).
  • the modified human IL-3 signal sequence which facilitates secretion of gene products outside of the cell, is flanked by a BamHI site on the 5' end and a unique NcoI site on the 3' end.
  • a unique HindIII site is 3' to the NcoI site and 5' to the poly-A sequence.
  • the DNA sequence encoding the signal peptide is shown below (restriction enzyme sites are indicated above).
  • the ATG (methionine) codon within the NcoI site is in-frame with the initiator ATG of the signal peptide (underlined); BamHI NcoI 5'GGATCCACCATGAGCCTGCCCGTCCTGCTCCTGCTCCAACTCCTGGTCCGCCCCGCCATGG (SEQ ID NO:255)
  • the single AflIII site was removed from pMON3934 by digestion with AflIII followed by filling in the overhangs by addition of a DNA polymerase and nucleotides.
  • the digested DNA fragment was purified via Magic PCR Clean up kit (Promega) and ligated with T4 DNA ligase.
  • the ligation reaction was transformed into DH5 ⁇ TM and the cells were plated onto LB-agar plus ampicillin. Individual colonies were screened for the loss of the AflIII site by restriction analysis with AflIII and HindIII which results in a single fragment if the AflIII site was removed.
  • the resulting plasmid was designated pMON30275.
  • the NcoI-HindIII fragment (ca. 425 bp) from pMON30245 was ligated to the NcoI-HindIII fragment (ca. 3800 bp) of the pMON30275.
  • pMON30245 (WO 94/12638) contains the gene coding for hIL-3 receptor agonist pMON13416 joined to a mouse IgG2b hinge fragment. Immediately 3' to the IgG2b hinge and 5' to the HindIII site is an AflIII site.
  • Genes can be cloned into the AflIII-HindIII sites as NcoI-HindIII or AflIII-HindIII fragments in frame with the hIL-3 variant pMON13416/IgG2b hinge to create novel chimeras.
  • the NcoI site and the AflIII site have compatible overhangs and will ligate but both recognition sites are lost.
  • RNA messenger RNA
  • the first strand cDNA reactions are carried out using a cDNA CycleTM Kit obtained from Invitrogen (San Diego, Calif.).
  • random primers and oligo dT primer are used to generate cDNA from a combination of human and fetal liver mRNA.
  • the RT product serves as the template for PCR with a combination of the primers, Forward primer: c-mplNcoI (SEQ ID NO:13) and Reverse primer: Ecompl.
  • the c-mplNcoI primer anneals to the c-mpl ligand gene (bases #279-311 based on c-mpl ligand sequence from Gene bank accession #L33410 or de Sauvage et al., Nature 369: 533-538 (1994)) and encodes a NcoI restriction enzyme site immediately 5' to the first codon (Ser+1) of c-mpl ligand.
  • the NcoI restriction enzyme site codes for methionine and alanine codons prior to Ser+1 and includes codon degeneracy for the Ala codon and the first four codons (Ser, Pro, Ala, & Pro) of c-mpl ligand.
  • the Ecompl primer anneals to bases #720-737 of c-mpl ligand and encodes an EcoRI site (GAATTC) in-frame with the c-mpl ligand gene immediately following Arg-153.
  • the EcoRI site creates Glu and Phe codons following Arg-153.
  • pMON3993 was a derivative of pMON3359 (described in Example 1).
  • the human IL-3 signal peptide sequence which had been subcloned as a BamHI fragment into the unique BamHI site between the IE110 promoter and poly-A signal, contains an NcoI site at its 3' end and is followed by a unique EcoRI site.
  • the RT reaction from Example 2 serves as the template for PCR with a combination of the following primers; c-mplNcoI (SEQ ID NO:13) (forward primer) and c-mplHindIII (SEQ ID NO:15) (reverse primer).
  • the c-mplNcoI (SEQ ID NO:13) primer is described in Example 2.
  • the c-mplHindIII (SEQ ID NO:15) primer which anneals to bases #716-737 of c-mpl ligand, adds both a termination codon and a HindIII restriction enzyme site immediately following the final codon, Arg 153 .
  • PCR products Two types are generated from the RT cDNA samples, one with a deletion of the codons for amino acids 112-115 and one without the deletion of these codons.
  • the c-mpl ligand PCR products (ca. 480 bp) are digested with NcoI and HindIII restriction enzymes for transfer to a mammalian expression vector, pMON3934.
  • pMON3934 is digested with NcoI and HindIII (ca. 3800 bp) and will accept the PCR products.
  • a PCR template for generating novel forms of c-mpl ligand is constructed by ligating the 3.7 Kbp BstXI/EcoRI fragment of pMON26458 to the 1 Kbp NcoI/BstXI fragment from pMON32133 (containing a deletion of amino acids 112-115) along with the EcoRI/AflIII 5L synthetic oligonucleotide linker 5L-5' (SEQ ID NO:18) and 5L-3' (SEQ ID NO:19).
  • the EcoRI end of the linker will ligate to the EcoRI end of pMON26458.
  • the AflIII end of the linker will ligate to the NcoI site of pMON32133, and neither restriction site will be retained upon ligation.
  • the BstXI sites of pMON26458 and pMON32133 will ligate as well.
  • Plasmid, pMON28548, is a result of the cloning and contains the DNA sequence of (SEQ ID NO:80) which encodes amino acids 1-153 c-mpl ligand fused via a GluPheGlyGlyAsnMetAla (SEQ ID NO:222) linker to amino acids 1-153 c-mpl ligand that contains a deletion of amino acids 112-115 (SEQ ID NO:162).
  • a PCR template for generating novel forms of c-mpl ligand is constructed by ligating the 3.7 Kbp BstXI/EcoRI fragment of pMON26458 to the 1 Kbp NcoI/BstXI fragment from pMON32132 along with the EcoRI/AflIII 4L synthetic oligonucleotide linker 4L-5' (SEQ ID NO:16) and 4L-3' (SEQ ID NO:17).
  • the EcoRI end of the linker will ligate to the EcoRI end of pMON26458.
  • the AflIII end of the linker will ligate to the NcoI site of pMON32132, and neither restriction site will be retained upon ligation.
  • the BstXI sites of pMON26458 and pMON32132 will ligate as well.
  • the plasmid, pMON28500 is a result of the cloning and contains the DNA sequence of (SEQ ID NO:82) which encodes amino acids 1-153 c-mpl ligand fused via a GluPheGlyAsnMetAla (SEQ ID NO:223) linker (4L) to amino acids 1-153 c-mpl ligand (SEQ ID NO:163).
  • a PCR template for generating novel forms of c-mpl ligand is constructed by ligating the 3.7 Kbp BstXI/EcoRI fragment of pMON26458 to the 1 Kbp NcoI/BstXI fragment from pMON32132 along with the EcoRI/AflIII 5L synthetic oligonucleotide linker 5L-5' (SEQ ID NO:18) and 5L-3' (SEQ ID NO:19).
  • Plasmid, pMON28501 is a result of the cloning and contains the DNA sequence of (SEQ ID NO: 82) which encodes amino acids 1-153 c-mpl ligand fused via a GluPheGlyGlyAsnMetAla (SEQ ID NO:222) linker (5L) to amino acids 1-153 c-mpl ligand (SEQ ID NO:164).
  • a PCR template for generating novel forms of c-mpl ligand is constructed by ligating the 3.7 Kbp BstXI/EcoRI fragment of pMON26458 to the 1 Kbp NcoI/BstXI fragment from pMON32134 along with the EcoRI/AflIII 8L synthetic oligonucleotide linker 8L-5' (SEQ ID NO:20) and 8L-3' (SEQ ID NO:21).
  • the EcoRI end of the linker will ligate to the EcoRI end of pMON26458.
  • the AflIII end of the linker will ligate to the NcoI site of pMON32134, and neither restriction site will be retained upon ligation.
  • the BstXI sites of pMON26458 and pMON32134 will ligate as well.
  • Plasmid, pMON28502 is a result of the cloning which contains the DNA sequence of (SEQ ID NO:83) and encodes amino acids 1-153 c-mpl ligand fused via a GluPheGlyGlyAsnGlyGlyAsnMetAla (SEQ ID NO:224) linker (8L) to amino acids 1-153 c-mpl ligand (SEQ ID NO:165).
  • the templates and oligonucleotide sets used in the PCR reactions are shown in Table 4.
  • the products that were generated were about 480 bp and were purified via Magic PCR Clean up kits (Promega).
  • the c-mpl receptor agonist gene PCR products were digested with NcoI and HindIII or AflIII and HindIII restriction enzymes (ca. 470 bp) for transfer to a mammalian expression vector.
  • the expression vector, pMON30304 was digested with NcoI and HindIII (ca. 4200 bp) and accepts the PCR products as NcoI-HindIII or AflIII-HindIII fragments.
  • the restriction digest of the PCR product and the resulting plasmids are shown in Table 4.
  • Plasmid pACYC177 (Chang, A. C. Y. and Cohen, S. N. J. Bacteriol. 134:1141-1156, 1978) DNA was digested with restriction enzymes HindIII and BamHI, resulting in a 3092 base pair HindIII, BamHI fragment. Plasmid, pMON13037 (WO 95/21254), DNA was digested with BglII and FspI, resulting in a 616 base pair BglII, FspI fragment.
  • Plasmid, pMON15960 DNA was digested with restriction enzyme SmaI and used as template in a PCR reaction using synthetic DNA oligonucleotides 38 stop (SEQ ID NO:65) and 39 start (SEQ ID NO:64) as primers, resulting in the amplification of a DNA fragment of 576 base pairs.
  • the amplified fragment was digested with restriction enzymes HindIII and NcoI, resulting in a HindIII, NcoI fragment of 558 base pairs.
  • Plasmid, pMON13181 DNA was digested with HindIII and AflIII, resulting in a HindIII, AflIII fragment of 4068 base pairs. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm the correct insert.
  • the plasmid, pMON15981 contains the DNA sequence of (SEQ ID NO:155) which encodes the following amino acid sequence:
  • Plasmid, pMON15960 DNA was digested with restriction enzyme SmaI and used as template in a PCR reaction using synthetic DNA oligonucleotides 96 stop (SEQ ID NO:67) and 97 start (SEQ ID NO:66) as primers, resulting in the amplification of a DNA fragment of 576 base pairs.
  • the amplified fragment was digested with restriction enzymes HindIII and NcoI, resulting in a HindIII, NcoI fragment of 558 base pairs.
  • Plasmid, pMON13181 DNA was digested with HindIII and AflIII, resulting in a HindIII, AflIII fragment of 4068 base pairs. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm the correct insert.
  • the plasmid, pMON15982 contains the DNA sequence of (SEQ ID NO:157) which encodes the following amino acid sequence:
  • Plasmid, pMON15960 DNA was digested with restriction enzyme SmaI and used as template in a PCR reaction using synthetic DNA oligonucleotides 142 stop (SEQ ID NO:73) and 141 start (SEQ ID NO:72) as primers, resulting in the amplification of a DNA fragment of 576 base pairs.
  • the amplified fragment was digested with restriction enzymes HindIII and NcoI, resulting in a HindIII, NcoI fragment of 558 base pairs.
  • Plasmid, pMON13181 DNA was digested with HindIII and AflIII, resulting in a HindIII, AflIII fragment of 4068 base pairs. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm the correct insert.
  • the plasmid, pMON15965 contains the DNA sequence of (SEQ ID NO:157) which encodes the following amino acid sequence:
  • Plasmid, pMON15960 DNA was digested with restriction enzyme SmaI and used as template in a PCR reaction using synthetic DNA oligonucleotides 126 stop (SEQ ID NO:68) and 125 start (SEQ ID NO:69) as primers, resulting in the amplification of a DNA fragment of 576 base pairs.
  • the amplified fragment was digested with restriction enzymes HindIII and NcoI, resulting in a HindIII, NcoI fragment of 558 base pairs.
  • Plasmid, pMON13181 DNA was digested with HindIII and AflIII, resulting in a HindIII, AflIII fragment of 4068 base pairs. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm the correct insert.
  • the plasmid, pMON15966 contains the DNA sequence of (SEQ ID NO:158) which encodes the following amino acid sequence:
  • Plasmid, pMON15960 DNA was digested with restriction enzyme SmaI and used as template in a PCR reaction using synthetic DNA oligonucleotides 132 stop (SEQ ID NO:71) and 133 start (SEQ ID NO:70) as primers, resulting in the amplification of a DNA fragment of 576 base pairs.
  • the amplified fragment was digested with restriction enzymes HindIII and NcoI, resulting in a HindIII, NcoI fragment of 558 base pairs.
  • Plasmid, pMON13181 DNA was digested with HindIII and AflIII, resulting in a HindIII, AflIII fragment of 4068 base pairs. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm the correct insert.
  • the plasmid, pMON15967 contains the DNA sequence of (SEQ ID NO: 159) which encodes the following amino acid sequence:
  • pMON13180 an intermediate plasmid used for constructing Dlasmids that contain DNA sequence encoding multi-functional hematopoietic receptor agonists.
  • Plasmid, pMON13046 (WO 95/21254), DNA was digested with restriction endonucleases XmaI and SnaBI, resulting in a 4018 base pair vector fragment.
  • the 4018 base pair XmaI-SnaBI fragment was purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.) in which the 25 base pair XmaI-SnaBI insert fragment is not retained.
  • the complimentary pair of synthetic oligonucleotides, glyxal (SEQ ID NO:74) and glyxa2 (SEQ ID NO:75) were designed to remove sequence encoding a factor Xa cleavage site.
  • oligonucleotides When properly assembled these oligonucleotides also result in XmaI and SnaBI ends.
  • the primers, Glyxa1 and glyxa2 were annealed in annealing buffer (20 mM Tris-HCl pH7.5, 10 mM MgCl 2 , 50 mM NaCl) by heating at 70° C. for ten minutes and allowed to slow cool.
  • the 4018 base pair XmaI-SnaBI fragment from pMON13046 was ligated with the assembled oligonucleotides using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E.
  • Plasmid DNA was isolated from the transformants and analyzed using a PCR based assay. Plasmid DNA from selected transformants was sequenced to confirm the correct insertion of the oligonucleotides. The resulting plasmid was designated pMON13180 and contains the DNA sequence of (SEQ ID NO:258).
  • pMON13181 an intermediate plasmid used for constructing plasmids that contain DNA sequences encoding multi-functional hematopoietic receptor agonists.
  • Plasmid, pMON13047 (WO 95/21254), DNA was digested with restriction endonucleases XmaI and SnaBI, resulting in a 4063 base pair vector fragment.
  • the 4063 base pair XmaI-SnaBI fragment was purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.) in which the 25 base pair XmaI-SnaBI insert fragment is not retained.
  • the complimentary pair of synthetic oligonucleotides, glyxal (SEQ ID NO:74) and glyxa2 (SEQ ID NO:75) were designed to remove sequence encoding the factor Xa cleavage site.
  • oligonucleotides When properly assembled these oligonucleotides also result in XmaI and SnaBI ends. Glyxal and glyxa2 were annealed in annealing buffer by heating at 70° C. for ten minutes and allowed to slow cool. The 4063 base pair XmaI-SnaBI fragment from pMON13047 was ligated with the assembled oligonucleotides using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates.
  • Plasmid DNA was isolated from the transformants and analyzed using a PCR based assay. Plasmid DNA from selected transformants was sequenced to confirm the correct insertion of the oligonucleotides. The resulting plasmid was designated pMON13181 and contains the DNA sequence of (SEQ ID NO:257).
  • the new N-terminus/C-terminus gene in pMON13182 was created using Method I as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 39 start (SEQ ID NO:64) and L-11 start (SEQ ID NO:60).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 38 stop (SEQ ID NO:65) and L-11 stop (SEQ ID NO:61).
  • the full-length new N terminus/C-terminus G-CSF Ser 17 gene was created and amplified from the annealed Fragments Start and Stop using primers 39 start and 38 stop.
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the intermediate plasmid, pMON13180 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13182.
  • E. coli strain JM101 was transformed with pMON13182 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13182 contains the DNA sequence of (SEQ ID NO:94) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13183 was created using Method I as described in Materials and Methods.
  • "Fragment Start” was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 39 start (SEQ ID NO:64) and L-11 start (SEQ ID NO:60).
  • Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 38 stop (SEQ ID NO:65) and L-l1 stop (SEQ ID NO:61).
  • the full-length new N terminus/C-terminus G-CSF Ser 17 gene was created and amplified from the annealed Fragments Start and Stop using 39 start and 38 stop.
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the intermediate plasmid, pMON13181 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13183.
  • E. coli strain JM101 was transformed with pMON13183 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13183 contains the DNA sequence of (SEQ ID NO:95) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13184 was created using Method I as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 97 start (SEQ ID NO:66) and L-11 start (SEQ ID NO:60).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 96 stop (SEQ ID NO:67) and L-11 stop (SEQ ID NO:61).
  • the full-length new N terminus/C-terminus G-CSF Ser 17 gene was created and amplified from the annealed Fragments Start and Stop using 97 start and 96 stop.
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the intermediate plasmid, pMON13180 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13184.
  • E. coli strain JM101 was transformed with pMON13184 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13184 contains the DNA sequence of (SEQ ID NO:96) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13185 was created using Method I as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 97 start (SEQ ID NO:66) and L-11 start (SEQ ID NO:60).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 96 stop (SEQ ID NO:67 and L-11 stop (SEQ ID NO:61).
  • the full-length new N terminus/C-terminus G-CSF Ser 17 gene was created and amplified from the annealed Fragments Start and Stop using 97 start and 96 stop.
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the intermediate plasmid, pMON13181 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13185.
  • E. coli strain JM101 was transformed with pMON13185 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13185 contains the DNA sequence of (SEQ ID NO:67) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13186 was created using Method I as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 126 start (SEQ ID NO:68) and L-11 start (SEQ ID NO:60).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 125 stop (SEQ ID NO:69) and L-11 stop (SEQ ID NO:61).
  • the full-length new N terminus/C-terminus G-CSF Ser 17 gene was created and amplified from the annealed Fragments Start and Stop using 126 start and 125 stop.
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the intermediate plasmid, pMON13180 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13186.
  • E. coli strain JM101 was transformed with pMON13186 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13186 contains the DNA sequence of (SEQ ID NO:98) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13187 was created using Method I as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 126 start (SEQ ID NO:68) and L-11 start (SEQ ID NO:60).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 125 stop (SEQ ID NO:69) and L-11 stop (SEQ ID NO:61).
  • the full-length new N terminus/C-terminus G-CSF Ser 17 gene was created and amplified from the annealed Fragments Start and Stop using 126 start and 125 stop.
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the intermediate plasmid, pMON13181 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13187.
  • E. coli strain JM101 was transformed with pMON13187 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13187 contains the DNA sequence of (SEQ ID NO:99) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13188 was created using Method I as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 133 start (SEQ ID NO:70) and L-11 start (SEQ ID NO:60).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 132 stop (SEQ ID NO:71) and L-11 stop (SEQ ID NO:61).
  • the full-length new N terminus/C-terminus G-CSF Ser 17 gene was created and amplified from the annealed Fragments Start and Stop using 133 start and 132 stop.
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the intermediate plasmid, pMON13180 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13188.
  • E. coli strain JM101 was transformed with pMON13188 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13188 contains the DNA sequence of (SEQ ID NO:100) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13189 was created using Method I as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 133 start (SEQ ID NO:70) and L-11 start (SEQ ID NO:60).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 132 stop (SEQ ID NO:71) and L-11 stop (SEQ ID NO:61).
  • the full-length new N terminus/C-terminus G-CSF Ser 17 gene was created and amplified from the annealed Fragments Start and Stop using 133 start and 132 stop.
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the intermediate plasmid, pMON13181 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13189.
  • E. coli strain JM101 was transformed with pMON13189 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13189 contains the DNA sequence of (SEQ ID NO:101) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13190 was created using Method I as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 142 start (SEQ ID NO:72) and L-11 start (SEQ ID NO:60).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 141 stop (SEQ ID NO:73) and L-11 stop (SEQ ID NO:61).
  • the full-length new N terminus/C-terminus G-CSF Ser 17 gene was created and amplified from the annealed Fragments Start and Stop using 142 start and 141 stop.
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the intermediate plasmid, pMON13180 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13190.
  • E. coli strain JM101 was transformed with pMON13190 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13190 contains the DNA sequence of (SEQ ID NO:102) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13191 was created using Method I as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 142 start (SEQ ID NO:72) and L-11 start (SEQ ID NO:60).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 141 stop (SEQ ID NO:73) and L-11 stop (SEQ ID NO:61).
  • the full-length new N terminus/C-terminus G-CSF Ser 17 gene was created and amplified from the annealed Fragments Start and Stop using 142 start and 141 stop.
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the intermediate plasmid, pMON13181 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13191.
  • E. coli strain JM101 was transformed with pMON13191 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13191 contains the DNA sequence of (SEQ ID NO:103) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13192 was created using Method II as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF sequence in pMON13037 using the primer set, 39 start (SEQ ID NO:64) and P-bl start (SEQ ID NO:62).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 38 stop (SEQ ID NO:65) and P-bl stop (SEQ ID NO:63).
  • Fragment Start was digested with restriction endonuclease NcoI
  • Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
  • the intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser 17 gene and was digested with restriction endonucleases NcoI and HindIII.
  • the digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser 17 gene was isolated using Geneclean (Bio101, Vista, Calif.).
  • the intermediate plasmid, pMON13180 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13192.
  • E. coli strain JM101 was transformed with pMON13192 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13192 contains the DNA sequence of (SEQ ID NO:104) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13193 was created using Method II as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 39 start (SEQ ID NO:64) and P-bl start (SEQ ID NO:62).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 38 stop (SEQ ID NO:65) and P-bl stop (SEQ ID NO:63).
  • Fragment Start was digested with restriction endonuclease NcoI
  • Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
  • the intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser 17 gene and was digested with restriction endonucleases NcoI and HindIII.
  • the digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser 17 gene was isolated using Geneclean (Bio101, Vista, Calif.).
  • the intermediate plasmid, pMON13181 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13193.
  • E. coli strain JM101 was transformed with pMON13193 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13193 contains the DNA sequence of (SEQ ID NO:105) encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON25190 was created using Method II as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF sequence in pMON13037 using the primer set, 97 start (SEQ ID NO:66) and P-bl start (SEQ ID NO:62).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 96 stop (SEQ ID NO:67) and P-bl stop (SEQ ID NO:63).
  • Fragment Start was digested with restriction endonuclease NcoI
  • Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
  • the intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser 17 gene and was digested with restriction endonucleases NcoI and HindIII.
  • the digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser 17 gene was isolated using Geneclean (Bio101, Vista, Calif.).
  • the intermediate plasmid, pMON13180 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON25190.
  • E. coli strain JM101 was transformed with pMON25190 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON25190 contains the DNA sequence of (SEQ ID NO:106) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON25191 was created using Method II as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 97 start (SEQ ID NO:66) and P-bl start (SEQ ID NO:62).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 96 stop (SEQ ID NO:98) and P-bl stop (SEQ ID NO:63).
  • Fragment Start was digested with restriction endonuclease NcoI
  • Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
  • the intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser 17 gene and was digested with restriction endonucleases NcoI and HindIII.
  • the digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser 17 gene was isolated using Geneclean (Bio101, Vista, Calif.).
  • the intermediate plasmid, pMON13181 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON25191.
  • E. coli strain JM101 was transformed with pMON25191 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON25191 contains the DNA sequence of (SEQ ID NO:107) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13194 was created using Method II as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 126 start (SEQ ID NO:68) and P-bl start (SEQ ID NO:62).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 125 stop (SEQ ID NO:67) and P-bl stop (SEQ ID NO:63).
  • Fragment Start was digested with restriction endonuclease NcoI
  • Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
  • the intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser 17 gene and was digested with restriction endonucleases NcoI and HindIII.
  • the digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser 17 gene was isolated using Geneclean (Bio101, Vista, Calif.).
  • the intermediate plasmid, pMON13180 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13194.
  • E. coli strain JM101 was transformed with pMON13194 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13194 contains the DNA sequence of (SEQ ID NO:108) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13195 was created using Method II as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 126 start (SEQ ID NO:68) and P-bl start (SEQ ID NO:62).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 125 stop (SEQ ID NO:69) and P-bl stop (SEQ ID NO:63).
  • Fragment Start was digested with restriction endonuclease NcoI
  • Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
  • the intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser 17 gene and was digested with restriction endonucleases NcoI and HindIII.
  • the digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser 17 gene was isolated using Geneclean (Bio101, Vista, Calif.).
  • the intermediate plasmid, pMON13181 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13195.
  • E. coli strain JM101 was transformed with pMON13195 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13195 contains the DNA sequence of (SEQ ID NO:109) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13196 was created using Method II as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF sequence in pMON13037 using the primer set, 133 start (SEQ ID NO:70) and P-bl start (SEQ ID NO:62).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 132 stop (SEQ ID NO:71) and P-bl stop (SEQ ID NO:63).
  • Fragment Start was digested with restriction endonuclease NcoI
  • Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
  • the intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser 17 gene and was digested with restriction endonucleases NcoI and HindIII.
  • the digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser 17 gene was isolated using Geneclean (Bio101, Vista, Calif.).
  • the intermediate plasmid, pMON13180 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13196.
  • E. coli strain JM101 was transformed with pMON13196 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13196 contains the DNA sequence of (SEQ ID NO:110) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13197 was created using Method II as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 133 start (SEQ ID NO:70) and P-bl start (SEQ ID NO:62).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 132 stop (SEQ ID NO:71) and P-bl stop (SEQ ID NO:63).
  • Fragment Start was digested with restriction endonuclease NcoI
  • Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
  • the intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser 17 gene and was digested with restriction endonucleases NcoI and HindIII.
  • the digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser 17 gene was isolated using Geneclean (Bio101, Vista, Calif.).
  • the intermediate plasmid, pMON13181 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13197.
  • E. coli strain JM101 was transformed with pMON13197 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13197 contains the DNA sequence of (SEQ ID NO:lll) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13198 was created using Method II as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF sequence in pMON13037 using the primer set, 142 start (SEQ ID NO:72) and P-bl start (SEQ ID NO:62).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 141 stop (SEQ ID NO:73) and P-bl stop (SEQ ID NO:63).
  • Fragment Start was digested with restriction endonuclease NcoI
  • Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
  • the intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser 17 gene and was digested with restriction endonucleases NcoI and HindIII.
  • the digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser 17 gene was isolated using Geneclean (Bio101, Vista, Calif.).
  • the intermediate plasmid, pMON13180 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13198.
  • E. coli strain JM101 was transformed with pMON13198 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13198 contains the DNA sequence of (SEQ ID NO:112) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON13199 was created using Method II as described in Materials and Methods.
  • Fragment Start was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 142 start (SEQ ID NO:72) and P-bl start (SEQ ID NO:62).
  • Fragment Stop was created and amplified from G-CSF Ser 17 sequence in pMON13037 using the primer set, 141 stop (SEQ ID NO:73) and P-bl stop (SEQ ID NO:63).
  • Fragment Start was digested with restriction endonuclease NcoI
  • Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
  • the intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser 17 gene and was digested with restriction endonucleases NcoI and HindIII.
  • the digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser 17 gene was isolated using Geneclean (Bio101, Vista, Calif.).
  • the intermediate plasmid, pMON13181 was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.).
  • the purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13199.
  • E. coli strain JM101 was transformed with pMON13199 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON13199 contains the DNA sequence of (SEQ ID NO:113) which encodes the following amino acid sequence:
  • hIL-3 receptor agonist pMON13416 To create the tandemly-duplicated hIL-3 receptor agonist pMON13416 template, syntan3, three DNAs were joined by means of ligation using T4 DNA ligase (Boehringer Mannheim).
  • the three DNAs are: 1) pMON13046, containing hIL-3 receptor agonist pMON13416, digested with BstEII and SnaBI; 2) the annealed complimentary pair of synthetic oligonucleotides, L3syn.for (SEQ ID NO:50) and L3syn.rev (SEQ ID NO:51), which contain sequence encoding the linker that connects the C-terminal and N-terminal ends of the original protein and a small amount of surrounding pMON13416 sequence and which when properly assembled result in BstEII and SnaBI ends; and 3) a portion of hIL-3 receptor agonist pMON13416 digested from pMON13046 with ClaI
  • E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Miniprep DNA was isolated from the transformants, and the transformants were screened using a PCR based assay. Plasmid DNA from selected transformants was sequenced to obtain the correct template. The resulting plasmid was designated syntan3 and contains the DNA sequence of (SEQ ID NO:85).
  • the new N-terminus/C-terminus gene in pMON31104 was created using Method III as described in Materials and Methods.
  • the full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan1, using the primer set 35 start (SEQ ID NO:52) and 34 rev (SEQ ID NO:53).
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI.
  • the digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.).
  • the purified digested DNA fragment was ligated into the expression vector,pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.).
  • the pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31104.
  • E. coli strain JM101 was transformed with pMON31104 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON31104 contains the DNA sequence of (SEQ ID NO:86) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON31105 was created using Method III as described in Materials and Methods.
  • the full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan1, using the primer set 70 start (SEQ ID NO:54) and 69 rev (SEQ ID NO:55).
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI.
  • the digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.).
  • the purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.).
  • the pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31105.
  • E. coli strain JM101 was transformed with pMON31105 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON31105 contains the DNA sequence of (SEQ ID NO:87) which encodes the protein with the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON31106 was created using Method III as described in Materials and Methods.
  • the full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan1, using the primer set 91 start (SEQ ID NO:56) and 90 rev (SEQ ID NO:57).
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI.
  • the digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.).
  • the purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.).
  • the pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31106.
  • E. coli strain JM101 was transformed with pMON31106 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON31106 contains the DNA sequence of (SEQ ID NO:80) which encodes the protein with the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON31107 was created using Method III as described in Materials and Methods.
  • the full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan1, using the primer set 101 start (SEQ ID NO:58) and 100 rev (SEQ ID NO:59).
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI.
  • the digested The DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.).
  • the purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.).
  • the pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31107.
  • E. coli strain JM101 was transformed with pMON31107 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON31107 contains the DNA sequence of (SEQ ID NO:89) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON31108 was created using Method III as described in Materials and Methods.
  • the full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan3, using the primer set 35 start (SEQ ID NO:52) and 34 rev (SEQ ID NO:53).
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI.
  • the digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.).
  • the purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.).
  • the pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31108.
  • E. coli strain JM101 was transformed with pMON31108 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON31108 contains the DNA sequence of (SEQ ID NO:90) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON31109 was created using Method III as described in Materials and Methods.
  • the full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan3, using the primer set 70 start (SEQ ID NO:54) and 69 rev (SEQ ID NO:55).
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI.
  • the digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.).
  • the purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.).
  • the pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31109.
  • E. coli strain JM101 was transformed with pMON31109 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON31109 contains the DNA sequence of (SEQ ID NO:91) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON31110 was created using Method III as described in Materials and Methods.
  • the full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan3, using the primer set 91 start (SEQ ID NO:56) and 90 rev (SEQ ID NO:57).
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI.
  • the digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.).
  • the purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.).
  • the pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31110.
  • E. coli strain JM101 was transformed with pMON31110 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON31110 contains the DNA sequence of (SEQ ID NO:92) which encodes the following amino acid sequence:
  • the new N-terminus/C-terminus gene in pMON31111 was created using Method III as described in Materials and Methods.
  • the full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan3, using the primer set 101 start (SEQ ID NO:58) and 100 rev (SEQ ID NO:59).
  • the resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI.
  • the digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.).
  • the purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.).
  • the pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5 ⁇ cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31111.
  • E. coli strain JM101 was transformed with pMON31111 for protein expression and protein isolation from inclusion bodies.
  • the plasmid, pMON31111 contains the DNA sequence of (SEQ ID NO:93) which encodes the following amino acid sequence:
  • Plasmid, pMON13189 DNA was digested with restriction enzymes NcoI and XmaI resulting in an NcoI, XmaI vector fragment that was isolated and purified from a 0.8% agarose gel.
  • the DNA from a second plasmid, pMON13222 (WO 94/12639, U.S. Ser. No. 08/411,796) was digested with NcoI and EcoRI resulting in a 281 base pair NcoI, EcoRI fragment.
  • This fragment was isolated and purified from a 1.0% agarose gel.
  • Two oligonucleotides SYNNOXA1.REQ (SEQ ID NO:240) and SYNNOXA2.REQ (SEQ ID NO:241) were annealed and ligated with the 281 base pair DNA fragment from pMON13222 to the DNA vector fragment from pMON13189. A portion of the ligation mixture was then transformed into E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis to show the presence of an EcoRV fragment, and sequenced to confirm the correct inserts.
  • the plasmid, pMON31112 contains the DNA sequence of (SEQ ID NO:114) which encodes the following amino acid sequence:
  • Plasmid, pMON13197 DNA was digested with restriction enzymes NcoI and XmaI resulting in an NcoI, XmaI vector fragment that was isolated and purified from a 0.8% agarose gel.
  • the DNA from a second plasmid, pMON13239 (WO 94/12639, U.S. Ser. No. 08/411,796) was digested with NcoI and EcoRI resulting in a 281 base pair NcoI, EcoRI fragment.
  • This fragment was isolated and purified from a 1.0% agarose gel.
  • Two oligonucleotides SYNNOXA1.REQ (SEQ ID NO:240) and SYNNOXA2.REQ (SEQ ID NO:241) were annealed and ligated with the 281 base pair DNA fragment from pMON13239 to the DNA vector fragment from pMON13197. A portion of the ligation mixture was then transformed into E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis to show the presence of an EcoRV fragment, and sequenced to confirm the correct inserts.
  • the plasmid, pMON31113 contains the DNA sequence of (SEQ ID NO:115) which encodes the following amino acid sequence:
  • Plasmid, pMON13189 DNA was digested with restriction enzymes NcoI and XmaI resulting in an NcoI, XmaI vector fragment that was isolated and purified from a 0.8% agarose gel.
  • the DNA from a second plasmid, pMON13239 (WO 94/12639, U.S. Ser. No. 08/411,796), was digested with NcoI and EcoRI resulting in a 281 base pair NcoI, EcoRI fragment.
  • This fragment was isolated and purified from a 1.0% agarose gel.
  • Two oligonucleotides SYNNOXA1.REQ (SEQ ID NO:240) and SYNNOXA2.REQ (SEQ ID NO:241) were annealed and ligated with the 281 base pair DNA fragment from pMON13239 to the DNA vector fragment from pMON13189. A portion of the ligation mixture was then transformed into E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis to show the presence of an EcoRV fragment, and sequenced to confirm the correct inserts.
  • the plasmid, pMON31114 contains the DNA sequence of (SEQ ID NO:116) which encodes the following amino acid sequence:
  • Plasmid, pMON13197 DNA was digested with restriction enzymes NcoI and XmaI resulting in an NcoI, XmaI vector fragment that was isolated and purified from a 0.8% agarose gel.
  • SYNNOXA1.REQ SEQ ID NO:240
  • SYNNOXA2.REQ SEQ ID NO:241
  • SEQ ID NO:241 Two oligonucleotides SYNNOXA1.REQ (SEQ ID NO:240) and SYNNOXA2.REQ (SEQ ID NO:241) were annealed and ligated with the 281 base pair DNA fragment from pMON13222 to the DNA vector fragment from pMON13197. A portion of the ligation mixture was then transformed into E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis to show the presence of an EcoRV fragment, and sequenced to confirm the correct inserts.
  • the plasmid, pMON31115 contains the DNA sequence of (SEQ ID NO:117) which encodes the following amino acid sequence:
  • the protein concentration of the multi-functional hematopoietic receptor agonist protein can be determined using a sandwich ELISA based on an affinity purified polyclonal antibody. Alternatively the protein concentration can be determined by amino acid composition analysis.
  • the bioactivity of the multi-functional hematopoietic receptor agonist can be determined in a number of in vitro assays. For example a multi-functional hematopoietic receptor agonist which binds the hIL-3 receptor and G-CSF receptor can be assayed in cell proliferation assays using cell lines expressing the hIL-3 and/or G-CSF receptors.
  • One such assay is the AML-193 cell proliferation assay. AML-193 cells respond to IL-3 and G-CSF which allows for the combined bioactivity of the IL-3/G-CSF multi-functional hematopoietic receptor agonist to be determined.
  • Another such assay is the TF1 cell proliferation assay.
  • factor dependent cell lines such as M-NFS-60 (ATCC. CRL 1838) or 32D which are murine IL-3 dependent cell line, may be used.
  • the activity of IL-3 is species specific whereas G-CSF is not, therefore the bioactivity of the G-CSF component of the IL-3/G-CSF multi-functional hematopoietic receptor agonist can be determined independently.
  • Cell lines, such as BHK or murine Baf/3 which do not express the receptor for a given ligand can be transfected with a plasmid containing a gene encoding the desired receptor.
  • An example of such a cell line is BaF3 transfected with the hG-CSF receptor (BaF3/hG-CSF).
  • the activity of the multi-functional hematopoietic receptor agonist in these cell lines can be compared with hIL-3 or G-CSF alone or together.
  • the bioactivity of examples of multi-functional hematopoietic receptor agonists of the present invention assayed in the BaF3/hG-CSF cell proliferation and TF1 cell proliferation assays is shown in Table 5 and Table 6.
  • the bioactivity of the multi-functional hematopoietic receptor agonist is expressed as relative activity compared with a standard protein pMON13056 (WO 95/21254).
  • the bioactivity of examples of multi-functional hematopoietic receptor agonists of the present invention assayed in the BaF3/c-mpl cell proliferation and TF1 cell proliferation assays is shown in Table 7 and Table 8.
  • the methylcellulose assay can be used to determine the effect of the multi-functional hematopoietic receptor agonists on the expansion of the hematopoietic progenitor cells and the pattern of the different types of hematopoietic colonies in vitro.
  • the methylcellulose assay can provide an estimate of precursor frequency since one measures the frequency of progenitors per 100,000 input cells. Long term, stromal dependent cultures have been used to delineate primitive hematopoietic progenitors and stem cells.
  • This assay can be used to determine whether the multi-functional hematopoietic receptor agonist stimulates the expansion of very primitive progenitors and/or stem cells.
  • limiting dilution cultures can be performed which will indicate the frequency of primitive progenitors stimulated by the multi-functional hematopoietic receptor agonist.
  • G-CSF variants which contain single or multiple amino acid substitutions were made using PCR mutagenesis techniques as described in WO 94/12639 and WO 94/12638. These and other variants (i.e. amino acid substitutions, insertions or deletions and N-terminal or C-terminal extensions) could also be made, by one skilled in the art, using a variety of other methods including synthetic gene assembly or site-directed mutagenesis (see Taylor et al., Nucl. Acids Res., 13: 7864-8785 [1985]; Kunkel et al., Proc. Natl. Acad. Sci.
  • G-CSF amino acid substitution variants include substitutions at positions 1 (Thr to Ser, Arg or Gly, 2 (Pro to Leu), 3 (Leu to Arg or Ser) and 17 (Cys to Ser) and deletions of amino acids 1-11 (Kuga et al. Biochemicla and Biophysical Research Comm. 159:103-111 (1989)).
  • G-CSF amino acid substitution variants can be used as the template to create the G-CSF receptor agonists in which a new N-terminus and new C-terminus are created. Examples of G-CSF amino acid substitution variants are shown in Table 9.
  • the G-CSF amino acid substitution variants can be assayed for cell proliferation activity using the Baf/3 cell line transfected with the human G-CSF receptor.
  • the bioactivity of examples of G-CSF amino acid substitution variants is shown in Table 9 relative to native human G-CSF. A "+” indicates a comparable activity to native and a "-" indicates significantly reduced or no measurable activity.
  • the multi-functional receptor agonists may comprise sequence rearranged c-mpl receptor agonist, which also have the substitution of the cysteine residues at position 7 and/or 151 with an another amino acid, which can be prepared by the methods described in Examples 1-89 and by other methods known to those skilled in the art.
  • One such c-mpl receptor agonist has the breakpoint at 115/116 and alanine at positions 7 and 151.
  • This c-mpl receptor agonist has the following amino acid:
  • ProGln (SEQ ID NO:284), and is encoded by the following DNA sequence;
  • Another c-mpl receptor agonist has the breakpoint at 81/82 and alanine at positions 7 and 151.
  • This c-mpl receptor agonist has the following amino acid;
  • GlnLeu (SEQ ID NO:285), and is encoded by the following DNA sequence;
  • the plasmids in Table 10 contain genes encoding multi-functional hematopoietic receptor agonists comprising a sequence rearranged G-CSF receptor agonists that were made by the method of Horlich et al (Protein Eng. 5:427-431, 1992). As described in Materials and Methods, the tandem repeat of the G-CSF Ser 17 gene was maintained on a pACYC177 based plasmid (Chang and Cohen, J. Bacteriol.

Abstract

Disclosed are novel multi-functional hematopoietic receptor agonist proteins, DNAs which encode the multi-functional hematopoietic receptor agonists proteins, methods of making the multi-functional hematopoietic receptor agonists proteins and methods of using the multi-functional hematopoietic receptor agonists proteins.

Description

The present application is a Continuation-in-Part of PCT/US 96/15774 filed Oct. 4, 1996 which claims priority under 35 USC §119(e) of U.S. provisional application Serial No. 60/004,834 filed Oct. 5, 1995.
FIELD OF THE INVENTION
The present invention relates to multi-functional hematopoietic receptor agonists.
BACKGROUND OF THE INVENTION
Colony stimulating factors (CSFs) which stimulate the differentiation and/or proliferation of bone marrow cells have generated much interest because of their therapeutic potential for restoring depressed levels of hematopoietic stem cell-derived cells. CSFs in both human and murine systems have been identified and distinguished according to their activities. For example, granulocyte-CSF (G-CSF) and macrophage-CSF (M-CSF) stimulate the in vitro formation of neutrophilic granulocyte and macrophage colonies, respectively, while GM-CSF and interleukin-3 (IL-3) have broader activities and stimulate the formation of both macrophage, neutrophilic and eosinophilic granulocyte colonies. IL-3 also stimulates the formation of mast, megakaryocyte and pure and mixed erythroid colonies.
U.S. Pat. No. 4,877,729 and U.S. Pat. No. 4,959,455 disclose human IL-3 and gibbon IL-3 cDNAs and the protein sequences for which they code. The hIL-3 disclosed has serine rather than proline at position 8 in the protein sequence.
International Patent Application (PCT) WO 88/00598 discloses gibbon- and human-like IL-3. The hIL-3 contains a Ser8 ->Pro8 replacement. Suggestions are made to replace Cys by Ser, thereby breaking the disulfide bridge, and to replace one or more amino acids at the glycosylation sites.
U.S. Pat. No. 4,810,643 discloses the DNA sequence encoding human G-CSF.
WO 91/02754 discloses a fusion protein comprised of GM-CSF and IL-3 which has increased biological activity compared to GM-CSF or IL-3 alone. Also disclosed are nonglycosylated IL-3 and GM-CSF analog proteins as components of the multi-functional hematopoietic receptor agonist.
WO 92/04455 discloses fusion proteins composed of IL-3 fused to a lymphokine selected from the group consisting of IL-3, IL-6, IL-7, IL-9, IL-11, EPO and G-CSF.
WO 95/21197 and WO 95/21254 disclose fusion proteins capable of broad multi-functional hematopoietic properties.
GB 2,285,446 relates to the c-mpl ligand (thrombopoietin) and various forms of thrombopoietin which are shown to influence the replication, differentiation and maturation of megakaryocytes and megakaryocytes progenitors which may be used for the treatment of thrombocytopenia.
EP 675,201 A1 relates to the c-mpl ligand (Megakaryocyte growth and development factor (MGDF), allelic variations of c-mpl ligand and c-mpl ligand attached to water soluble polymers such as polyethylene glycol.
WO 95/21920 provides the murine and human c-mpl ligand and polypeptide fragments thereof. The proteins are useful for in vivo and ex vivo therapy for stimulating platelet production.
Rearrangement of Protein Sequences
In evolution, rearrangements of DNA sequences serve an important role in generating a diversity of protein structure and function. Gene duplication and exon shuffling provide an important mechanism to rapidly generate diversity and thereby provide organisms with a competitive advantage, especially since the basal mutation rate is low (Doolittle, Protein Science 1: 191-200, 1992).
The development of recombinant DNA methods has made it possible to study the effects of sequence transposition on protein folding, structure and function. The approach used in creating new sequences resembles that of naturally occurring pairs of proteins that are related by linear reorganization of their amino acid sequences (Cunningham, et al., Proc. Natl. Acad. Sci. U.S.A. 76: 3218-3222, 1979; Teather & Erfle, J. Bacteriol. 172: 3837-3841, 1990; Schimming et al., Eur. J. Biochem. 204: 13-19, 1992; Yamiuchi and Minamikawa, FEBS Lett. 260: 127-130, 1991; MacGregor et al., FEBS Lett. 378: 263-266). The first in vitro application of this type of rearrangement to proteins was described by Goldenberg and Creighton (J. Mol. Biol. 165: 407-413, 1983). A new N-terminus is selected at an internal site (breakpoint) of the original sequence, the new sequence having the same order of amino acids as the original from the breakpoint until it reaches an amino acid that is at or near the original C-terminus. At this point the new sequence is joined, either directly or through an additional portion of sequence (linker), to an amino acid that is at or near the original N-terminus, and the new sequence continues with the same sequence as the original until it reaches a point that is at or near the amino acid that was N-terminal to the breakpoint site of the original sequence, this residue forming the new C-terminus of the chain.
This approach has been applied to proteins which range in size from 58 to 462 amino acids (Goldenberg & Creighton, J. Mol. Biol. 165: 407-413, 1983; Li & Coffino, Mol. Cell. Biol. 13: 2377-2383, 1993). The proteins examined have represented a broad range of structural classes, including proteins that contain predominantly α-helix (interleukin-4; Kreitman et al., Cytokine 7: 311-318, 1995), β-sheet (interleukin-1; Horlick et al., Protein Eng. 5: 427-431, 1992), or mixtures of the two (yeast phosphoribosyl anthranilate isomerase; Luger et al., Science 243: 206-210, 1989). Broad categories of protein function are represented in these sequence reorganization studies:
Enzymes
T4 lysozyme Zhang et al., Biochemistry 32: 12311-12318, 1993; Zhang et al., Nature Struct. Biol. 1: 434-438 (1995)
dihydrofolate reductase Buchwalder et al., Biochemistry 31: 1621-1630, 1994; Protasova et al., Prot. Eng. 7: 1373-1377, 1995)
ribonuclease T1 Mullins et al., J. Am. Chem. Soc. 116: 5529-5533, 1994; Garrett et al., Protein Science 5: 204-211, 1996)
Bacillus β-glucanse Hahn et al., Proc. Natl. Acad. Sci. U.S.A. 91: 10417-10421, 1994)
aspartate transcarbamoylase Yang & Schachman, Proc. Natl. Acad. Sci. U.S.A. 90: 11980-11984, 1993)
phosphoribosyl anthranilate isomerase Luger et al., Science 243: 206-210 (1989; Luger et al., Prot. Eng. 3: 249-258, 1990)
pepsin/pepsinogen Lin et al., Protein Science 4: 159-166, 1995)
glyceraldehyde-3-phosphate dehydrogenase Vignais et al., Protein Science 4: 994-1000, 1995)
ornithine decarboxylase Li & Coffino, Mol. Cell. Biol. 13: 2377-2383, 1993)
yeast phosphoglycerate dehydrogenase Ritco-Vonsovici et al., Biochemistry 34: 16543-16551, 1995)
Enzyme Inhibitor
basic pancreatic trypsin inhibitor Goldenberg & Creighton, J. Mol. Biol. 165: 407-413, 1983)
Cytokines
interleukin-1β Horlick et al., Protein Eng. 5: 427-431, 1992)
interleukin-4 Kreitman et al., Cytokine 7: 311-318, 1995)
Tyrosine Kinase Recognition Domain
α-spectrin SH3 domain Viguera, et al., J. Mol. Biol. 247: 670-681, 1995)
Transmembrane Protein
omp A Koebnik & Kramer, J. Mol. Biol. 250: 617-626, 1995)
Chimeric Protein
interleukin-4-Pseudomonas exotoxin Kreitman et al., Proc. Natl. Acad. Sci. U.S.A. 91: 6889-6893, 1994).
The results of these studies have been highly variable. In many cases substantially lower activity, solubility or thermodynamic stability were observed (E. coli dihydrofolate reductase, aspartate transcarbamoylase, phosphoribosyl anthranilate isomerase, glyceraldehyde-3-phosphate dehydrogenase, ornithine decarboxylase, omp A, yeast phosphoglycerate dehydrogenase). In other cases, the sequence rearranged protein appeared to have many nearly identical properties as its natural counterpart (basic pancreatic trypsin inhibitor, T4 lysozyme, ribonuclease T1, Bacillus β-glucanase, interleukin-1β, α-spectrin SH3 domain, pepsinogen, interleukin-4). In exceptional cases, an unexpected improvement over some properties of the natural sequence was observed, e.g., the solubility and refolding rate for rearranged α-spectrin SH3 domain sequences, and the receptor affinity and anti-tumor activity of transposed interleukin-4-Pseudomonas exotoxin fusion molecule (Kreitman et al., Proc. Natl. Acad. Sci. U.S.A. 91: 6889-6893, 1994; Kreitman et al., Cancer Res. 55: 3357-3363, 1995).
The primary motivation for these types of studies has been to study the role of short-range and long-range interactions in protein folding and stability. Sequence rearrangements of this type convert a subset of interactions that are long-range in the original sequence into short-range interactions in the new sequence, and vice versa. The fact that many of these sequence rearrangements are able to attain a conformation with at least some activity is persuasive evidence that protein folding occurs by multiple folding pathways (Viguera, et al., J. Mol. Biol. 247: 670-681, 1995). In the case of the SH3 domain of a-spectrin, choosing new termini at locations that corresponded to β-hairpin turns resulted in proteins with slightly less stability, but which were nevertheless able to fold.
The positions of the internal breakpoints used in the studies cited here are found exclusively on the surface of proteins, and are distributed throughout the linear sequence without any obvious bias towards the ends or the middle (the variation in the relative distance from the original N-terminus to the breakpoint is ca. 10 to 80% of the total sequence length). The linkers connecting the original N- and C-termini in these studies have ranged from 0 to 9 residues. In one case (Yang & Schachman, Proc. Natl. Acad. Sci. U.S.A. 90: 11980-11984, 1993), a portion of sequence has been deleted from the original C-terminal segment, and the connection made from the truncated C-terminus to the original N-terminus. Flexible hydrophilic residues such as Gly and Ser are frequently used in the linkers. Viguera, et al. (J. Mol. Biol. 247: 670-681, 1995) compared joining the original N- and C-termini with 3- or 4-residue linkers; the 3-residue linker was less thermodynamically stable. Protasova et al. (Protein Eng. 7: 1373-1377, 1994) used 3- or 5-residue linkers in connecting the original N-termini of E. coli dihydrofolate reductase; only the 3-residue linker produced protein in good yield.
SUMMARY OF THE INVENTION
Novel hematopoietic proteins of this invention are represented by the formulas:
R.sub.1 -L.sub.1 -R.sub.2, R.sub.2 -L.sub.1 -R.sub.1, R.sub.1 -R.sub.2, or R.sub.2 -R.sub.1
wherein R1 and R2 are independently selected from the group consisting of;
(I) A polypeptide comprising; a modified human G-CSF amino acid sequence of the formula:
1                                   10                                    
Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa                       
                        20                                                
Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly               
    30                                      40                            
Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa               
                        50                                                
Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp               
    60                                      70                            
Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly               
                        80                                                
Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu               
    90                                      100                           
Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu               
                        110                                               
Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp               
    120                                     130                           
Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr               
                        140                                               
Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala               
    150                                     160                           
Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa               
                        170                                               
Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro (SEQ ID NO:1)
wherein
Xaa at position 1 is Thr, Ser, Arg, Tyr or Gly;
Xaa at position 2 is Pro or Leu;
Xaa at position 3 is Leu, Arg, Tyr or Ser;
Xaa at position 13 is Phe, Ser, His, Thr or Pro;
Xaa at position 16 is Lys, Pro, Ser, Thr or His;
Xaa at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg;
Xaa at position 18 is Leu, Thr, Pro, His, Ile or Cys;
Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala;
Xaa at position 24 is Ile, Pro, Tyr or Leu;
Xaa at position 27 is Asp, or Gly;
Xaa at position 30 is Ala, Ile, Leu or Gly;
Xaa at position 34 is Lys or Ser;
Xaa at position 36 is Cys or Ser;
Xaa at position 42 is Cys or Ser;
Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu;
Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln, or Thr;
Xaa at position 46 is Glu, Arg, Phe, Arg, Ile or Ala;
Xaa at position 47 is Leu or Thr;
Xaa at position 49 is Leu, Phe, Arg or Ser;
Xaa at position 50 is Leu, Ile, His, Pro or Tyr;
Xaa at position 54 is Leu or His;
Xaa at position 64 is Cys or Ser;
Xaa at position 67 is Gln, Lys, Leu or Cys;
Xaa at position 70 is Gln, Pro, Leu, Arg or Ser;
Xaa at position 74 is Cys or Ser;
Xaa at position 104 is Asp, Gly or Val;
Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly;
Xaa at position 115 is Thr, His, Leu or Ala;
Xaa at position 120 is Gln, Gly, Arg, Lys or His
Xaa at position 123 is Glu, Arg, Phe or Thr
Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu;
Xaa at position 146 is Arg or Gln;
Xaa at position 147 is Arg or Gln;
Xaa at position 156 is His, Gly or Ser;
Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly;
Xaa at position 162 is Glu, Leu, Gly or Trp;
Xaa at position 163 is Val, Gly, Arg or Ala;
Xaa at position 169 is Arg, Ser, Leu, Arg or Cys;
Xaa at position 170 is His, Arg or Ser;
wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can be deleted; and
wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;
______________________________________                                    
39-40          63-64       124-125                                        
40-41                                     125-126                         
41-42                                     126-127                         
42-43                                     128-129                         
43-44                                     128-129                         
45-46                                     129-130                         
48-49                                     130-131                         
49-50                                     131-132                         
52-53                                     132-133                         
53-54                                     133-134                         
54-55                                     134-135                         
55-56                                     135-136                         
56-57                                     136-137                         
57-58                                     137-138                         
58-59                                     138-139                         
59-60                                     139-140                         
60-61                                     140-141                         
61-62                                    141-142                          
                           or 142-143;                                    
______________________________________
(II) A polypeptide comprising; a modified hIL-3 amino acid sequence of the formula:
Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn               
1               5                   10                  15                
Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa               
                20                  25                  30                
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa               
                35                  40                  45                
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa               
                50                  55                  60                
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa               
                65                  70                  75                
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa               
                80                  85                  90                
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa               
                95                  100                 105               
Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa               
                110                 115                 120               
Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe                       
                125                 130   (SEQ ID NO:2);
wherein
Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
Xaa at position 36 is Asp, Leu, or Val;
Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
Xaa at position 38 is Asn, or Ala;
Xaa at position 40 is Leu, Trp, or Arg;
Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
Xaa at position 57 is Asn or Gly;
Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
Xaa at position 85 is Leu, Asn, Val, or Gln;
Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
Xaa at position 87 is Leu, Ser, Trp, or Gly;
Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln;
Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
Xaa at position 103 is Asp, or Ser;
Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp;
Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;
Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
wherein optionally from 1 to 14 amino acids can be deleted from the N-terminus and/or from 1 to 15 amino acids can be deleted from the C-terminus; and wherein from 0 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; and
wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;
______________________________________                                    
26-27          49-50       83-84                                          
27-28                                       84-85                         
28-29                                       85-86                         
29-30                                       86-87                         
30-31                                       87-88                         
31-32                                       88-89                         
32-33                                       89-90                         
33-34                                       90-91                         
34-35                                       91-92                         
35-36                                       92-93                         
36-37                                       97-98                         
37-38                                       98-99                         
38-39                                       99-100                        
39-40                                       100-101                       
40-41                                       101-102                       
41-42                                       102-103                       
                           or 103-104;                                    
______________________________________
or
(III) A polypeptide comprising; a modified human c-mpl ligand amino acid sequence of the formula:
 SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer                 
1           5              10             15                              
HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro                 
20             25             30             35                           
ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu                 
   40             45             50             55                        
ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla                 
      60             65             70             75                     
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly                 
         80             85             90             95                  
GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa                 
            100            105            110                             
XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis                 
115            120            125            130                          
LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal                 
   135            140            145            150                       
ArgArgAlaProProThrThrAlaValProSerArgThrSerLeuValLeuThrLeu                 
      155            160            165            170                    
AsnGluLeuProAsnArgThrSerGlyLeuLeuGluThrAsnPheThrAlaSerAla                 
         175            180            185            190                 
ArgThrThrGlySerGlyLeuLeuLysTrpGlnGlnGlyPheArgAlaLysIlePro                 
            195            200            205                             
GlyLeuLeuAsnGlnThrSerArgSerLeuAspGlnIleProGlyTyrLeuAsnArg                 
210            215            220            225                          
IleHisGluLeuLeuAsnGlyThrArgGlyLeuPheProGlyProSerArgArgThr                 
   230            235            240            245                       
LeuGlyAlaProAspIleSerSerGlyThrSerAspThrGlySerLeuProProAsn                 
      250            255            260            265                    
LeuGlnProGlyTyrSerProSerProThrHisProProThrGlyGlnTyrThrLeu                 
         270            275            280            285                 
PheProLeuProProThrLeuProThrProValValGlnLeuHisProLeuLeuPro                 
            290            295            300                             
AspProSerAlaProThrProThrProThrSerProLeuLeuAsnThrSerTyrThr                 
305            310            315            320                          
HisSerGlnAsnLeuSerGlnGluGly (SEQ ID NO:3)                                 
   325            330   332                                               
153
wherein;
Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met;
Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn; and
wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;
______________________________________                                    
26-27          51-52       108-109                                        
27-28                                       109-110                       
28-29                                       110-111                       
29-30                                       111-112                       
30-31                                       112-113                       
32-33                                       113-114                       
33-34                                       114-115                       
34-35                                       115-116                       
36-37                                       116-117                       
37-38                                       117-118                       
38-39                                       118-119                       
40-41                                       119-120                       
41-42                                       120-121                       
42-43                                       121-122                       
43-44                                       122-123                       
44-45                                       123-124                       
46-47                                       124-125                       
47-48                                       125-126                       
48-49                                       126-127                       
50-51                                       or 127-128;                   
______________________________________
or
(IV) A polypeptide comprising; a modified hIL-3 amino acid sequence of the formula:
Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn               
1               5                   10                  15                
Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa               
                20                  25                  30                
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa               
                35                  40                  45                
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa               
                50                  55                  60                
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa               
                65                  70                  75                
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa               
                80                  85                  90                
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa               
                95                  100                 105               
Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa               
                110                 115                 120               
Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe                       
                125                 130 (SEQ ID NO:2)
wherein
Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
Xaa at position 36 is Asp, Leu, or Val;
Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
Xaa at position 38 is Asn, or Ala;
Xaa at position 40 is Leu, Trp, or Arg;
Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or
Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
Xaa at position 57 is Asn or Gly;
Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
Xaa at position 85 is Leu, Asn, Val, or Gln;
Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
Xaa at position 87 is Leu, Ser, Trp, or Gly;
Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln;
Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
Xaa at position 103 is Asp, or Ser;
Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp;
Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;
Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
wherein optionally from 1 to 14 amino acids can be deleted from the N-terminus and/or from 1 to 15 amino acids can be deleted from the C-terminus; and wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; or
(V) a colony stimulating factor;
and wherein L1 is a linker capable of linking R1 to R2 ;
with the proviso that at least R1 or R2 is selected from the polypeptide of formula (I) , (II), or (III); and
said hematopoietic protein can optionally be immediately preceded by (methionine-1), (alanine-1) or (methionine-2, alanine-1).
The more preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (I) above are; 38-39, 39-40, 40-41, 41-42, 48-49, 53-54, 54-55, 55-56, 56-57, 57-58, 58-59, 59-60, 60-61, 61-62, 62-63, 64-65, 65-66, 66-67, 67-68, 68-69, 69-70, 96-97, 125-126, 126-127, 127-128, 128-129, 129-130, 130-131, 131-132, 132-133, 133-134, 134-135, 135-136, 136-137, 137-138, 138-139, 139-140, 140-141 and 141-142.
The most preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (I) above are; 38-39, 48-49, 96-97, 125-126, 132-133 and 141-142.
The more preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (II) above are; 28-29, 29-30, 30-31, 31-32, 32-33, 33-34, 34-35, 35-36, 36-37, 37-38, 38-39, 39-40, 66-67, 67-68, 68-69, 69-70, 70-71, 84-85, 85-86, 86-87, 87-88, 88-89, 89-90, 90-91, 98-99, 99-100, 100-101 and 101-102.
The most preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (II) above are; 34-35, 69-70 and 90-91.
The more preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (III) above or the amino acid sequence of (SEQ ID NO:256) are; 80-81, 81-82, 82-83, 83-84, 84-85, 85-86, 86-87, 108-109, 109-110, 110-111, 111-112, 112-113, 113-114, 114-115, 115-116, 116-117, 117-118, 118-119, 119-120, 120-121, 121-122, 122-123, 123-124, 124-125, 125-126 and 126-127.
The most preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (III) above or the amino acid sequence of (SEQ ID NO:256) are; 81-82, 108-109, 115-116, 119-120, 122-123 and 125-126.
The invention is also intended to include multifunctional receptor agonists which comprises a sequence rearranged c-mpl receptor agonist in which the cysteine at position 7 and/or 151 are substituted with another amino acid. Preferably, the substitution at position 7 and 151 is Ser, Ala, Gly, His, Asn, Asp, Thr, Phe or Thr. More preferably, the substitution at position 7 and 151 is Ser, Ala, Gly, His or Asn.
The multifunctional receptor agonist of the present invention can also be represented by the following formula:
(T.sup.1)a-(L.sup.1)b-X.sup.1 -(L)c-X.sup.2 -(L.sup.2)d-(T.sup.2)e
X.sup.1 -(L)c-X.sup.2 -(L)-Y.sup.1 -(L)c-Y.sup.2
in which:
X1 is a peptide comprising an amino acid sequence corresponding to the sequence of residues n+1 through J of the original protein having amino acids residues numbered sequentially 1 through J with an amino terminus at residue 1;
L is an optional linker;
X2 is a peptide comprising an amino acid sequence of residues 1 through n of the original protein;
Y1 is a peptide comprising an amino acid sequence corresponding to the sequence of residues n=1 through K of the original protein having amino acids residues numbered sequentially 1 through K with an amino terminus at residue 1;
Y2 is a peptide comprising an amino acid sequence of residues 1 through n of the original protein;
L1 and L2 are optional peptide spacers:
n is an integer ranging from 1 to J-1;
b, c, and d are each independently 0 or 1;
a and e are either 0 or 1, provided that both a and e cannot both be 0; and
T1 and T2 are proteins.
Additionally, the present invention relates to recombinant expression vectors comprising nucleotide sequences encoding the multi-functional hematopoietic receptor agonists, related microbial expression systems, and processes for making the multi-functional hematopoietic receptor agonists. The invention also relates to pharmaceutical compositions containing the multi-functional hematopoietic receptor agonists, and methods for using the multi-functional hematopoietic receptor agonists.
In addition to the use of the multi-functional hematopoietic receptor agonists of the present invention in vivo, it is envisioned that in vitro uses would include the ability to stimulate bone marrow and blood cell activation and growth before infusion into patients.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 schematically illustrates the sequence rearrangement of a protein. The N-terminus (N) and the C-terminus (C) of the native protein are joined through a linker, or joined directly. The protein is opened at a breakpoint creating a new N-terminus (new N) and a new C-terminus (new-C) resulting in a protein with a new linear amino acid sequence. A rearranged molecule may be synthesized de novo as linear molecule and not go through the steps of joining the original N-terminus and the C-terminus and opening of the protein at the breakpoint.
FIG. 2 shows a schematic of Method I, for creating new proteins in which the original N-terminus and C-terminus of the native protein are joined with a linker and different N-terminus and C-terminus of the protein are created. In the example shown the sequence rearrangement results in a new gene encoding a protein with a new N-terminus created at amino acid 97 of the original protein, the original C-terminus (a.a. 174) joined to the amino acid 11 (a.a. 1-10 are deleted) through a linker region and a new C-terminus created at amino acid 96 of the original sequence.
FIG. 3 shows a schematic of Method II, for creating new proteins in which the original N-terminus and C-terminus of the native protein are joined without a linker and different N-terminus and C-terminus of the protein are created. In the example shown the sequence rearrangement results in a new gene encoding a protein with a new N-terminus created at amino acid 97 of the original protein, the original C-terminus (a.a. 174) joined to the original N-terminus and a new C-terminus created at amino acid 96 of the original sequence.
FIG. 4 shows a schematic of Method III, for creating new proteins in which the original N-terminus and C-terminus of the native protein are joined with a linker and different N-terminus and C-terminus of the protein are created. In the example shown the sequence rearrangement results in a new gene encoding a protein with a new N-terminus created at amino acid 97 of the original protein, the original C-terminus (a.a. 174) joined to amino acid 1 through a linker region and a new C-terminus created at amino acid 96 of the original sequence.
DETAILED DESCRIPTION OF THE INVENTION
The present invention encompasses multi-functional hematopoietic receptor agonists formed from covalently linked polypeptides, each of which may act through a different and specific cell receptor to initiate complementary biological activities. Hematopoiesis requires a complex series of cellular events in which stem cells generate continuously into large populations of maturing cells in all major lineages. There are currently at least 20 known regulators with hematopoietic proliferative activity. Most of these proliferative regulators can only stimulate one or another type of colony formation in vitro, the precise pattern of colony formation stimulated by each regulator is quite distinctive. No two regulators stimulate exactly the same pattern of colony formation, as evaluated by colony numbers or, more importantly, by the lineage and maturation pattern of the cells making up the developing colonies. Proliferative responses can most readily be analyzed in simplified in vitro culture systems. Three quite different parameters can be distinguished: alteration in colony size, alteration in colony numbers and cell lineage. Two or more factors may act on the progenitor cell, inducing the formation of larger number of progeny thereby increasing the colony size. Two or more factors may allow increased number of progenitor cells to proliferate either because distinct subsets of progenitors cells exist that respond exclusively to one factor or because some progenitors require stimulation by two or more factors before being able to respond. Activation of additional receptors on a cell by the use of two or more factors is likely to enhance the mitotic signal because of coalescence of initially differing signal pathways into a common final pathway reaching the nucleus (Metcalf, Nature 339: 27, 1989). Other mechanisms could explain synergy. For example, if one signaling pathway is limited by an intermediate activation of an additional signaling pathway which is caused by a second factor, then this may result in a super additive response. In some cases, activation of one receptor type can induce an enhanced expression of other receptors (Metcalf, Blood 82: 3515-3523, 1993). Two or more factors may result in a different pattern of cell lineages than from a single factor. The use of multi-functional hematopoietic receptor agonists may have a potential clinical advantage resulting from a proliferative response that is not possible by any single factor.
The receptors of hematopoietic and other growth factors can be grouped into two distinct families of related proteins: (1) tyrosine kinase receptors, including those for epidermal growth factor, M-CSF (Sherr, Blood 75: 1, 1990) and SCF (Yarden et al., EMBO J. 6: 3341, 1987): and (2) hematopoietic receptors, not containing a tyrosine kinase domain, but exhibiting obvious homology in their extracellular domain (Bazan, PNAS USA 87: 6934-6938, 1990). Included in this latter group are erythropoietin (EPO) (D'Andrea et al., Cell 57: 277, 1989), GM-CSF (Gearing et al., EMBO J. 8: 3667, 1989), IL-3 (Kitamura et al., Cell 66: 1165, 1991), G-CSF (Fukunaga et al., J. Bio. Chem. 265: 14008-15, 1990), IL-4 (Harada et al., PNAS USA 87: 857, 1990), IL-5 (Takaki et al., EMBO J. 9: 4367, 1990), IL-6 (Yamasaki et al., Science 241: 825, 1988), IL-7 (Goodwin et al., Cell 60: 941-51, 1990), LIF (Gearing et al., EMBO J. 10: 2839, 1991) and IL-2 (Cosman et al., Mol-Immunol. 23: 935-94, 1986). Most of the latter group of receptors exists in a high-affinity form as heterodimers. After ligand binding, the specific α-chains become associated with at least one other receptor chain (β-chain, γ-chain). Many of these factors share a common receptor subunit. The α-chains for GM-CSF, IL-3 and IL-5 share the same β-chain (Kitamura et al., Cell 66: 1165, 1991), Takaki et al., EMBO J. 10: 2833-8, 1991) and receptor complexes for IL-6, LIF and IL-11 share a common β-chain (gp130) (Taga et al., Cell 58: 573-81, 1989; Gearing et al., Science 255: 1434-7, 1992). The receptor complexes of IL-2, IL-4, IL-7, IL-9 and IL-15 share a common γ-chain (Kondo et al., Science 262: 1874, 1993; Russell et al., Science 266: 1042-1045, 1993; Noguchi et al., Science 262: 1877, 1993; Giri et al., EMBO J. 13: 2822-2830, 1994).
The use of a multiply acting hematopoietic factor may also have a potential advantage by reducing the demands placed on factor-producing cells and their induction systems. If there are limitations in the ability of a cell to produce a factor, then by lowering the required concentrations of each of the factors, and using them in combination may usefully reduce demands on the factor-producing cells. The use of a multiply acting hematopoietic factor may lower the amount of the factors that would be needed, probably reducing the likelihood of adverse side-effects.
Novel compounds of this invention are represented by a formula selected from the group consisting of:
R.sub.1 -L.sub.1 -R.sub.2, R.sub.2 -L.sub.1 -R.sub.1, R.sub.1 -R.sub.2, and R.sub.2 -R.sub.1
Where R1 and R2 are as defined above. R2 is preferably a colony stimulating factor with a different but complementary activity than R1. By complementary activity is meant activity which enhances or changes the response to another cell modulator. The R1 polypeptide is joined either directly or through a linker segment to the R2 polypeptide. The term "directly" defines multi-functional hematopoietic receptor agonists in which the polypeptides are joined without a peptide linker. Thus L1 represents a chemical bond or polypeptide segment to which both R1 and R2 are joined in frame, most commonly L1 is a linear peptide to which R1 and R2 are joined by amide bonds linking the carboxy terminus of R1 to the amino terminus of L1 and carboxy terminus of L1 to the amino terminus of R2. By "joined in frame" is meant that there is no translation termination or disruption between the reading frames of the DNA encoding R1 and R2.
A non-exclusive list of other growth factors, i.e. colony stimulating factors (CSFs), are cytokines, lymphokines, interleukins, hematopoietic growth factors which can be joined to (I), (II) or (III) include GM-CSF, G-CSF, c-mpl ligand (also known as TPO or MGDF), M-CSF, erythropoietin (EPO), IL-1, IL-4, IL-2, IL-3, IL-5, IL 6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-15, LIF, flt3 ligand, human growth hormone, and stem cell factor (SCF) also known as steel factor or c-kit ligand. Additionally, this invention encompasses the use of modified R1 or R2 molecules or mutated or modified DNA sequences encoding these R1 or R2 molecules. The present invention also includes multi-functional hematopoietic receptor agonists in which R1 or R2 is an hIL-3 variant, c-mpl ligand variant, or G-CSF variant. A "hIL-3 variant" is defined as a hIL-3 molecule which has amino acid substitutions and/or portions of hIL-3 deleted as disclosed in WO 94/12638, WO 94/12639 and WO 95/00646, as well as other variants known in the art. A "c-mpl ligand variant" is defined an c-mpl ligand molecule which has amino acid substitutions and/or portions of c-mpl ligand deleted, disclosed in U.S. application Ser. No. 08/383,035 as well as other variants known in the art. A "G-CSF variant" is defined an G-CSF molecule which has amino acid substitutions and/or portions of G-CSF deleted, as disclosed herein, as well as other variants known in the art.
The linking group (Li) is generally a polypeptide of between 1 and 500 amino acids in length. The linkers joining the two molecules are preferably designed to (1) allow the two molecules to fold and act independently of each other, (2) not have a propensity for developing an ordered secondary structure which could interfere with the functional domains of the two proteins, (3) have minimal hydrophobic characteristics which could interact with the functional protein domains and (4) provide steric separation of R1 and R2 such that R1 and R2 could interact simultaneously with their corresponding receptors on a single cell. Typically surface amino acids in flexible protein regions include Gly, Asn and Ser. Virtually any permutation of amino acid sequences containing Gly, Asn and Ser would be expected to satisfy the above criteria for a linker sequence. Other neutral amino acids, such as Thr and Ala, may also be used in the linker sequence. Additional amino acids may also be included in the linkers due to the addition of unique restriction sites in the linker sequence to facilitate construction of the multi-functional hematopoietic receptor agonists.
Preferred L1 linkers of the present invention include sequences selected from the group of formulas: (Gly3 Ser)n (SEQ ID NO:4), (Gly4 Ser)n (SEQ ID NO:5), (Gly5 Ser)n (SEQ ID NO:6), (Glyn Ser)n (SEQ ID NO:7) or (AlaGlySer)n (SEQ ID NO:8).
One example of a highly-flexible linker is the glycine and serine-rich spacer region present within the pIII protein of the filamentous bacteriophages, e.g. bacteriophages M13 or fd (Schaller et al., PNAS USA 72: 737-741, 1975). This region provides a long, flexible spacer region between two domains of the pIII surface protein. The spacer region consists of the amino acid sequence:
GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGluGlyGlyGlySerGluGlyGlyGlySerGluGlyGlyGlySerGluGlyGlyGlySerGlyGlyGlySer                          (SEQ ID NO:9).
The present invention also includes linkers in which an endopeptidase recognition sequence is included. Such a cleavage site may be valuable to separate the individual components of the multi-functional hematopoietic receptor agonist to determine if they are properly folded and active in vitro. Examples of various endopeptidases include, but are not limited to, plasmin, enterokinase, kallikrein, urokinase, tissue plasminogen activator, clostripain, chymosin, collagenase, Russell's viper venom protease, postproline cleavage enzyme, V8 protease, Thrombin and factor Xa.
Peptide linker segments from the hinge region of heavy chain immunoglobulins IgG, IgA, IgM, IgD or IgE provide an angular relationship between the attached polypeptides. Especially useful are those hinge regions where the cysteines are replaced with serines. Preferred linkers of the present invention include sequences derived from murine IgG gamma 2b hinge region in which the cysteines have been changed to serines. These linkers may also include an endopeptidase cleavage site. Examples of such linkers include the following sequences:
IleSerGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerPro (SEQ ID NO:10)
and
IleGluGlyArgIleSerGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerPro                                                  (SEQ ID NO:11).
The present invention is, however, not limited by the form, size or number of linker sequences employed and the only requirement of the linker is that functionally it does not interfere with the folding and function of the individual molecules of the multi-functional hematopoietic receptor agonist.
One aspect of the invention includes multi-functional hematopoietic receptor agonists which comprise a sequence rearranged c-mpl receptor agonist in which the cysteine(s) at position 7 and 151 of c-mpl ligand, have been substituted with another amino acid. Kaushansky et al. (Blood 86: 255a Abstract 1008, 1995) teaches that all four of the cysteines at positions 7, 29, 85, and 151 are required for bioactivity. The presence of cysteines in a protein can cause problems in processing when the protein is being produced recombinantly in a bacterial host. Microbially produced cysteine-containing proteins may tend to form multimers which greatly complicate purification of the protein product. Several additional purification steps, such as reduction and reoxidation of the recombinant protein may be required to obtain the protein in the proper confirmation. Removal of one of the cysteine residues, with concurrent replacement by a chemically equivalent neutral amino acid, would be desirable, in order to simplify the isolation and purification of the molecule. However, the successful removal of cysteines from biologically active molecules is unpredictable, in that the tertiary structure in the absence of the normally formed disulfide bridges, can be substantially altered. A molecule in which a pair of cysteines at positions 7 and 151 are substituted with another amino acid may have one or more advantages including, but not limited to: 1) increased folding efficiency of the heterologously expressed protein; 2) elimination of mispaired disulfides, 3) use of milder refold conditions (ie. Guanidine vs. Urea); 4) increased purification yields, 5) increased protein solubility; and 6) increased protein stability.
Determination of the Linker L2
The length of the amino acid sequence of the linker L2 to be used in R1 and/or R2 can be selected empirically or with guidance from structural information, or by using a combination of the two approaches.
When no structural information is available, a small series of linkers can be prepared for testing using a design whose length is varied in order to span a range from 0 to 50 Å and whose sequence is chosen in order to be consistent with surface exposure (hydrophilicity, Hopp & Woods, Mol. Immunol. 20: 483-489, 1983), Kyte & Doolittle, J. Mol. Biol. 157: 105-132; solvent exposed surface area, Lee & Richards, J. Mol. Biol. 55: 379-400, 1971) and the ability to adopt the necessary conformation with out deranging the conformation of R1 or R2 (conformationally flexible; Karplus & Schulz, Naturwissenschaften 72: 212-213, 1985). Assuming an average of translation of 2.0 to 3.8 Å per residue, this would mean the length to test would be between 0 to 30 residues, with 0 to 15 residues being the preferred range. Exemplary of such an empirical series would be to construct linkers using a cassette sequence such as Gly-Gly-Gly-Ser (SEQ ID NO:12) repeated n times, where n is 1, 2, 3 or 4. Those skilled in the art will recognize that there are many such sequences that vary in length or composition that can serve as linkers with the primary consideration being that they be neither excessively long nor short (cf., Sandhu, Critical Rev. Biotech. 12: 437-462, 1992); if they are too long, entropy effects will likely destabilize the three-dimensional fold, and may also make folding kinetically impractical, and if they are too short, they will likely destabilize the molecule because of torsional or steric strain.
Those skilled in the analysis of protein structural information will recognize that using the distance between the chain ends, defined as the distance between the c-alpha carbons, can be used to define the length of the sequence to be used, or at least to limit the number of possibilities that must be tested in an empirical selection of linkers. They will also recognize that it is sometimes the case that the positions of the ends of the polypeptide chain are ill-defined in structural models derived from x-ray diffraction or nuclear magnetic resonance spectroscopy data, and that when true, this situation will therefore need to be taken into account in order to properly estimate the length of the linker required. From those residues whose positions are well defined are selected two residues that are close in sequence to the chain ends, and the distance between their c-alpha carbons is used to calculate an approximate length for a linker between them. Using the calculated length as a guide, linkers with a range of number of residues (calculated using 2 to 3.8 Å per residue) are then selected. These linkers may be composed of the original sequence, shortened or lengthened as necessary, and when lengthened the additional residues may be chosen to be flexible and hydrophilic as described above; or optionally the original sequence may be substituted for using a series of linkers, one example being the Gly-Gly-Gly-Ser (SEQ ID NO:12) cassette approach mentioned above; or optionally a combination of the original sequence and new sequence having the appropriate total length may be used.
Determination of the Amino and Carboxyl Termini of R1 and R2
Sequences of R1 and R2 capable of folding to biologically active states can be prepared by appropriate selection of the beginning (amino terminus) and ending (carboxyl terminus) positions from within the original polypeptide chain while using the linker sequence L2 as described above. Amino and carboxyl termini are selected from within a common stretch of sequence, referred to as a breakpoint region, using the guidelines described below. A novel amino acid sequence is thus generated by selecting amino and carboxyl termini from within the same breakpoint region. In many cases the selection of the new termini will be such that the original position of the carboxyl terminus immediately preceded that of the amino terminus. However, those skilled in the art will recognize that selections of termini anywhere within the region may function, and that these will effectively lead to either deletions or additions to the amino or carboxyl portions of the new sequence.
It is a central tenet of molecular biology that the primary amino acid sequence of a protein dictates folding to the three-dimensional structure necessary for expression of its biological function. Methods are known to those skilled in the art to obtain and interpret three-dimensional structural information using x-ray diffraction of single protein crystals or nuclear magnetic resonance spectroscopy of protein solutions. Examples of structural information that are relevant to the identification of breakpoint regions include the location and type of protein secondary structure (alpha and 3-10 helices, parallel and anti-parallel beta sheets, chain reversals and turns, and loops; Kabsch & Sander, Biopolymers 22: 2577-2637, 1983), the degree of solvent exposure of amino acid residues, the extent and type of interactions of residues with one another (Chothia, Ann. Rev. Biochem. 53: 537-572, 1984) and the static and dynamic distribution of conformations along the polypeptide chain (Alber & Mathews, Methods Enzymol. 154: 511-533, 1987). In some cases additional information is known about solvent exposure of residues; one example is a site of post-translational attachment of carbohydrate which is necessarily on the surface of the protein. When experimental structural information is not available, or is not feasible to obtain, methods are also available to analyze the primary amino acid sequence in order to make predictions of protein tertiary and secondary structure, solvent accessibility and the occurrence of turns and loops. Biochemical methods are also sometimes applicable for empirically determining surface exposure when direct structural methods are not feasible; for example, using the identification of sites of chain scission following limited proteolysis in order to infer surface exposure (Gentile & Salvatore, Eur. J. Biochem. 218: 603-621, 1993) Thus using either the experimentally derived structural information or predictive methods (e.g., Srinivisan & Rose Proteins: Struct., Funct. & Genetics, 22: 81-99, 1995) the parental amino acid sequence is inspected to classify regions according to whether or not they are integral to the maintenance of secondary and tertiary structure. The occurrence of sequences within regions that are known to be involved in periodic secondary structure (alpha and 3-10 helices, parallel and anti-parallel beta sheets) are regions that should be avoided. Similarly, regions of amino acid sequence that are observed or predicted to have a low degree of solvent exposure are more likely to be part of the so-called hydrophobic core of the protein and should also be avoided for selection of amino and carboxyl termini. In contrast, those regions that are known or predicted to be in surface turns or loops, and especially those regions that are known not to be required for biological activity, are the preferred sites for location of the extremes of the polypeptide chain. Continuous stretches of amino acid sequence that are preferred based on the above criteria are referred to as a breakpoint region.
Non-covalent Multifunctional hematopoietic growth factors
An alternative method for connecting two hematopoietic growth factors is by means of a non-covalent interaction. Such complexed proteins can be described by one of the formulae:
R.sub.1 -C.sub.1 +R.sub.2 -C.sub.2 ; or C.sub.1 -R.sub.1 +C.sub.2 -R.sub.2 ; C.sub.1 -R.sub.1 +R.sub.2 -C.sub.2 ; or C.sub.1 -R.sub.1 +R.sub.2 -C.sub.2.
R1 and R2 are as is defined above. Domains C1 and C2 are either identical or non-identical chemical structures, typically proteinaceous, which can form a non-covalent, specific association. Complexes between C1 and C2 result in a one-to-one stoichiometric relationship between R1 and R2 for each complex. Examples of domains which associate are "leucine zipper" domains of transcription factors, dimerization domains of bacterial transcription repressors and immunoglobulin constant domains. Covalent bonds link R1 and C1, and R2 and C2, respectively. As indicated in the formulae, the domains C1 and C2 can be present either at the N-terminus or C-terminus of their corresponding hematopoietic growth factor (R). These multimerization domains (C1 and C2) include those derived from the bZIP family of proteins (Abel et al., Nature 341: 24-25, 1989; Landshulz et al., Science 240: 1759-1764, 1988; Pu et al., Nuc. Acid Res. 21: 4348-4355, 1993; Kozarides et al., Nature 336: 646-651, 1988), as well as multimerization domains of the helix-loop-helix family of proteins (Abel et al., Nature 341: 24-25, 1989; Murre et al., Cell 56: 777-783, 1989; Tapscott et al., Science 242: 405-411, 1988; Fisher et al., Genes & Dev. 5: 2342-2352, 1991). Preferred multi-functional hematopoietic receptor agonists of the present invention include colony stimulating factors dimerized by virtue of their incorporation as translational multi-functional hematopoietic receptor agonists with the leucine zipper dimerization domains of the bZIP family proteins Fos and Jun. The leucine zipper domain of Jun is capable of interacting with identical domains. On the other hand, the leucine zipper domain of Fos interacts with the Jun leucine zipper domain, but does not interact with other Fos leucine zipper domains. Mixtures of Fos and Jun predominantly result in formation of Fos-Jun heterodimers. Consequently, when joined to colony stimulating factors, the Jun domain can be used to direct the formation of either homo- or heterodimers. Preferential formation of heterodimers can be achieved if one of the colony stimulating factor partners is engineered to possess the Jun leucine zipper domain while the other is engineered to possess the Fos zipper.
Additional peptide sequences may also be added to facilitate purification or identification of multi-functional hematopoietic receptor agonist proteins (e.g., poly-His). A highly antigenic peptide may also be added that would enable rapid assay and facile purification of the multi-functional hematopoietic receptor agonist protein by a specific monoclonal antibody.
"Mutant amino acid sequence," "mutant protein", "variant protein", "mutein", or "mutant polypeptide" refers to a polypeptide having an amino acid sequence which varies from a native sequence due to amino acid deletions, substitutions, or both, or is encoded by a nucleotide sequence intentionally made variant from a native sequence. "Native sequence" refers to an amino acid or nucleic acid sequence which is identical to a wild-type or native form of a gene or protein.
Hematopoietic growth factors can be characterized by their ability to stimulate colony formation by human hematopoietic progenitor cells. The colonies formed include erythroid, granulocyte, megakaryocyte, granulocytic macrophages and mixtures thereof. Many of the hematopoietic growth factors have demonstrated the ability to restore bone marrow function and peripheral blood cell populations to therapeutically beneficial levels in studies performed initially in primates and subsequently in humans. Many or all of these biological activities of hematopoietic growth factors involve signal transduction and high affinity receptor binding. Multi-functional hematopoietic receptor agonists of the present invention may exhibit useful properties such as having similar or greater biological activity when compared to a single factor or by having improved half-life or decreased adverse side effects, or a combination of these properties.
Multi-functional hematopoietic receptor agonists which have little or no agonist activity maybe useful as antagonists, as antigens for the production of antibodies for use in immunology or immunotherapy, as genetic probes or as intermediates used to construct other useful hIL-3 muteins.
Biological activity of the multi-functional hematopoietic receptor agonist proteins of the present invention can be determined by DNA synthesis in factor-dependent cell lines or by counting the colony forming units in an in vitro bone marrow assay.
The multi-functional hematopoietic receptor agonists of the present invention may have an improved therapeutic profile as compared to single acting hematopoietic agonists. For example, some multi-functional hematopoietic receptor agonists of the present invention may have a similar or more potent growth factor activity relative to other hematopoietic agonists without having a similar or corresponding increase in side-effects.
The present invention also includes the DNA sequences which code for the multi-functional hematopoietic receptor agonist proteins, DNA sequences which are substantially similar and perform substantially the same function, and DNA sequences which differ from the DNAs encoding the multi-functional hematopoietic receptor agonists of the invention only due to the degeneracy of the genetic code. Also included in the present invention are the oligonucleotide intermediates used to construct the mutant DNAs and the polypeptides coded for by these oligonucleotides.
Genetic engineering techniques now standard in the art (U.S. Pat. No. 4,935,233 and Sambrook et al., "Molecular Cloning A Laboratory Manual", Cold Spring Harbor Laboratory, 1989) may be used in the construction of the DNA sequences of the present invention. One such method is cassette mutagenesis (Wells et al., Gene 34: 315-323, 1985) in which a portion of the coding sequence in a plasmid is replaced with synthetic oligonucleotides that encode the desired amino acid substitutions in a portion of the gene between two restriction sites.
Pairs of complementary synthetic oligonucleotides encoding the desired gene can be made and annealed to each other. The DNA sequence of the oligonucleotide would encode sequence for amino acids of desired gene with the exception of those substituted and/or deleted from the sequence.
Plasmid DNA can be treated with the chosen restriction endonucleases then ligated to the annealed oligonucleotides. The ligated mixtures can be used to transform competent JM101 cells to resistance to an appropriate antibiotic. Single colonies can be picked and the plasmid DNA examined by restriction analysis and/or DNA sequencing to identify plasmids with the desired genes.
Cloning of the DNA sequences of the novel multifunctional hematopoietic agonists wherein at least one of the with the DNA sequence of the other colony stimulating factor may be accomplished by the use of intermediate vectors. Alternatively one gene can be cloned directly into a vector containing the other gene. Linkers and adapters can be used for joining the DNA sequences, as well as replacing lost sequences, where a restriction site was internal to the region of interest. Thus genetic material (DNA) encoding one polypeptide, peptide linker, and the other polypeptide is inserted into a suitable expression vector which is used to transform bacteria, yeast, insect cells or mammalian cells. The transformed organism is grown and the protein isolated by standard techniques. The resulting product is therefore a new protein which has a colony stimulating factor joined by a linker region to a second colony stimulating factor.
Another aspect of the present invention provides plasmid DNA vectors for use in the expression of these novel multi-functional hematopoietic receptor agonists. These vectors contain the novel DNA sequences described above which code for the novel polypeptides of the invention. Appropriate vectors which can transform microorganisms capable of expressing the multi-functional hematopoietic receptor agonists include expression vectors comprising nucleotide sequences coding for the multi-functional hematopoietic receptor agonists joined to transcriptional and translational regulatory sequences which are selected according to the host cells used.
Vectors incorporating modified sequences as described above are included in the present invention and are useful in the production of the multi-functional hematopoietic receptor agonist polypeptides. The vector employed in the method also contains selected regulatory sequences in operative association with the DNA coding sequences of the invention and which are capable of directing the replication and expression thereof in selected host cells.
As another aspect of the present invention, there is provided a method for producing the novel multi-functional hematopoietic receptor agonists. The method of the present invention involves culturing suitable cells or cell line, which has been transformed with a vector containing a DNA sequence coding for expression of a novel multi-functional hematopoietic receptor agonist. Suitable cells or cell lines may be bacterial cells. For example, the various strains of E. coli are well-known as host cells in the field of biotechnology. Examples of such strains include E. coli strains JM101 (Yanish-Perron et al. Gene 33: 103-119, 1985) and MON105 (Obukowicz et al., Applied Environmental Microbiology 58: 1511-1523, 1992). Also included in the present invention is the expression of the multi-functional hematopoietic receptor agonist protein utilizing a chromosomal expression vector for E. coli based on the bacteriophage Mu (Weinberg et al., Gene 126: 25-33, 1993). Various strains of B. subtilis may also be employed in this method. Many strains of yeast cells known to those skilled in the art are also available as host cells for expression of the polypeptides of the present invention. When expressed in the E. coli cytoplasm, the gene encoding the multi-functional hematopoietic receptor agonists of the present invention may also be constructed such that at the 5' end of the gene codons are added to encode Met-2 -Ala-1 - or Met-1 at the N-terminus of the protein. The N termini of proteins made in the cytoplasm of E. coli are affected by post-translational processing by methionine aminopeptidase (Ben Bassat et al., J. Bac. 169: 751-757, 1987) and possibly by other peptidases so that upon expression the methionine is cleaved off the N-terminus. The multi-functional hematopoietic receptor agonists of the present invention may include multi-functional hematopoietic receptor agonist polypeptides having Met-1, Ala-1 or Met-2 -Ala-1 at the N-terminus. These mutant multi-functional hematopoietic receptor agonists may also be expressed in E. coli by fusing a secretion signal peptide to the N-terminus. This signal peptide is cleaved from the polypeptide as part of the secretion process.
Also suitable for use in the present invention are mammalian cells, such as Chinese hamster ovary cells (CHO). General methods for expression of foreign genes in mammalian cells are reviewed in Kaufman, R. J., 1987) Genetic Engineering, Principles and Methods, Vol. 9, J. K. Setlow, editor, Plenum Press, New York. An expression vector is constructed in which a strong promoter capable of functioning in mammalian cells drives transcription of a eukaryotic secretion signal peptide coding region, which is translationally joined to the coding region for the multi-functional hematopoietic receptor agonist. For example, plasmids such as pcDNA I/Neo, pRc/RSV, and pRc/CMV (obtained from Invitrogen Corp., San Diego, Calif.) can be used. The eukaryotic secretion signal peptide coding region can be from the gene itself or it can be from another secreted mammalian protein (Bayne, M. L. et al., Proc. Natl. Acad. Sci. USA 84: 2638-2642, 1987). After construction of the vector containing the gene, the vector DNA is transfected into mammalian cells. Such cells can be, for example, the COS7, HeLa, BHK, CHO, or mouse L lines. The cells can be cultured, for example, in DMEM media (JRH Scientific). The polypeptide secreted into the media can be recovered by standard biochemical approaches following transient expression for 24-72 hours after transfection of the cells or after establishment of stable cell lines following selection for antibiotic resistance. The selection of suitable mammalian host cells and methods for transformation, culture, amplification, screening and product production and purification are known in the art. See, e.g., Gething and Sambrook, Nature, 293: 620-625, 1981), or alternatively, Kaufman et al, Mol. Cell. Biol., 5 (7): 1750-1759, 1985) or Howley et al., U.S. Pat. No. 4,419,446. Another suitable mammalian cell line is the monkey COS-1 cell line. A similarly useful mammalian cell line is the CV-1 cell line.
Where desired, insect cells may be utilized as host cells in the method of the present invention. See, e.g., Miller et al., Genetic Engineering, 8: 277-298 (Plenum Press 1986) and references cited therein. In addition, general methods for expression of foreign genes in insect cells using Baculovirus vectors are described in: Summers, M. D. and Smith, G. E., 1987)--A manual of methods for Baculovirus vectors and insect cell culture procedures, Texas Agricultural Experiment Station Bulletin No. 1555. An expression vector is constructed comprising a Baculovirus transfer vector, in which a strong Baculovirus promoter (such as the polyhedron promoter) drives transcription of a eukaryotic secretion signal peptide coding region, which is translationally joined to the coding region for the multi-functional hematopoietic receptor agonist polypeptide. For example, the plasmid pVL1392 (obtained from Invitrogen Corp., San Diego, Calif.) can be used. After construction of the vector carrying the gene encoding the multi-functional hematopoietic receptor agonist polypeptide, two micrograms of this DNA is co-transfected with one microgram of Baculovirus DNA (see Summers & Smith, 1987) into insect cells, strain SF9. Pure recombinant Baculovirus carrying the multi-functional hematopoietic receptor agonist is used to infect cells cultured, for example, in Excell 401 serum-free medium (JRH Biosciences, Lenexa, Kans.). The multi-functional hematopoietic receptor agonist secreted into the medium can be recovered by standard biochemical approaches. Supernatants from mammalian or insect cells expressing the multi-functional hematopoietic receptor agonist protein can be first concentrated using any of a number of commercial concentration units.
The multi-functional hematopoietic receptor agonists of the present invention may be useful in the treatment of diseases characterized by decreased levels of either myeloid, erythroid, lymphoid, or megakaryocyte cells of the hematopoietic system or combinations thereof. In addition, they may be used to activate mature myeloid and/or lymphoid cells. Among conditions susceptible to treatment with the polypeptides of the present invention is leukopenia, a reduction in the number of circulating leukocytes (white cells) in the peripheral blood. Leukopenia may be induced by exposure to certain viruses or to radiation. It is often a side effect of various forms of cancer therapy, e.g., exposure to chemotherapeutic drugs, radiation and of infection or hemorrhage. Therapeutic treatment of leukopenia with these multi-functional hematopoietic receptor agonists of the present invention may avoid undesirable side effects caused by treatment with presently available drugs.
The multi-functional hematopoietic receptor agonists of the present invention may be useful in the treatment of neutropenia and, for example, in the treatment of such conditions as aplastic anemia, cyclic neutropenia, idiopathic neutropenia, Chediak-Higashi syndrome, systemic lupus erythematosus (SLE), leukemia, myelodysplastic syndrome and myelofibrosis.
The multi-functional hematopoietic receptor agonist of the present invention may be useful in the treatment or prevention of thrombocytopenia. Currently the only therapy for thrombocytopenia is platelet transfusion which are costly and carry the significant risks of infection (HIV, HBV) and alloimmunization. The multi-functional hematopoietic receptor agonist may alleviate or diminish the need for platelet transfusion. Severe thrombocytopenia may result from genetic defects such as Fanconi's Anemia, Wiscott-Aldrich, or May Hegglin syndromes. Acquired. thrombocytopenia may result from auto- or allo-antibodies as in Immune Thrombocytopenia Purpura, Systemic Lupus Erythromatosis, hemolytic anemia, or fetal maternal incompatibility. In addition, splenomegaly, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, infection or prosthetic heart valves may result in thrombocytopenia. Severe thrombocytopenia may also result from chemotherapy and/or radiation therapy or cancer. Thrombocytopenia may also result from marrow invasion by carcinoma, lymphoma, leukemia or fibrosis.
The multi-functional hematopoietic receptor agonists of the present invention may be useful in the mobilization of hematopoietic progenitors and stem cells in peripheral blood. Peripheral blood derived progenitors have been shown to be effective in reconstituting patients in the setting of autologous marrow transplantation. Hematopoietic growth factors including G-CSF and GM-CSF have been shown to enhance the number of circulating progenitors and stem cells in the peripheral blood. This has simplified the procedure for peripheral stem cell collection and dramatically decreased the cost of the procedure by decreasing the number of pheresis required. The multi-functional hematopoietic receptor agonist may be useful in mobilization of stem cells and further enhance the efficacy of peripheral stem cell transplantation.
The multi-functional hematopoietic receptor agonists of the present invention may also be useful in the ex vivo expansion of hematopoietic progenitors and stem cells. Colony stimulating factors (CSFs), such as hIL-3, have been administered alone, co-administered with other CSFs, or in combination with bone marrow transplants subsequent to high dose chemotherapy to treat the neutropenia and thrombocytopenia which are often the result of such treatment. However the period of severe neutropenia and thrombocytopenia may not be totally eliminated. The myeloid lineage, which is comprised of monocytes (macrophages), granulocytes (including neutrophils) and megakaryocytes, is critical in preventing infections and bleeding which can be life-threatening. Neutropenia and thrombocytopenia may also be the result of disease, genetic disorders, drugs, toxins, radiation and many therapeutic treatments such as conventional oncology therapy.
Bone marrow transplants have been used to treat this patient population. However, several problems are associated with the use of bone marrow to reconstitute a compromised hematopoietic system including: 1) the number of stem cells in bone marrow, spleen, or peripheral blood is limited, 2) Graft Versus Host Disease, 3) graft rejection and 4) possible contamination with tumor cells. Stem cells make up a very small percentage of the nucleated cells in the bone marrow, spleen and peripheral blood. It is clear that a dose response exists such that a greater number of stem cells will enhance hematopoietic recovery. Therefore, the in vitro expansion of stem cells should enhance hematopoietic recovery and patient survival. Bone marrow from an allogeneic donor has been used to provide bone marrow for transplant. However, Graft Versus Host Disease and graft rejection limit bone marrow transplantation even in recipients with HLA-matched sibling donors. An alternative to allogeneic bone marrow transplants is autologous bone marrow transplants. In autologous bone marrow transplants, some of the patient's own marrow is harvested prior to myeloablative therapy, e.g. high dose chemotherapy, and is transplanted back into the patient afterwards. Autologous transplants eliminate the risk of Graft Versus Host Disease and graft rejection. However, autologous bone marrow transplants still present problems in terms of the limited number of stems cells in the marrow and possible contamination with tumor cells. The limited number of stem cells may be overcome by ex-vivo expansion of the stem cells. In addition, stem cells can be specifically isolated, based on the presence of specific surface antigens such as CD34+ in order to decrease tumor cell contamination of the marrow graft.
The following patents contain further details on separating stem cells, CD34+ cells, culturing the cells with hematopoietic factors, the use of the cells for the treatment of patients with hematopoietic disorders and the use of hematopoietic factors for cell expansion and gene therapy.
U.S. Pat. No. 5,061,620 relates to compositions comprising human hematopoietic stem cells provided by separating the stem cells from dedicated cells.
U.S. Pat. No. 5,199,942 describes a method for autologous hematopoietic cell transplantation comprising: (1) obtaining hematopoietic progenitor cells from a patient; (2) ex-vivo expansion of cells with a growth factor selected from the group consisting of IL-3, flt3 ligand, c-kit ligand, GM-CSF, IL-1, GM-CSF/IL-3 fusion protein and combinations thereof; (3) administering cellular preparation to a patient.
U.S. Pat. No. 5,240,856 relates to a cell separator that includes an apparatus for automatically controlling the cell separation process.
WO 91/16116 describes devices and methods for selectively isolating and separating target cells from a mixture of cells.
WO 91/18972 describes methods for in vitro culturing of bone marrow, by incubating suspension of bone marrow cells, using a hollow fiber bioreactor.
WO 92/18615 relates to a process for maintaining and expanding bone marrow cells, in a culture medium containing specific mixtures of cytokines, for use in transplants.
WO 93/08268 describes a method for selectively expanding stem cells, comprising the steps of (a) separating CD34+ stem cells from other cells and (b) incubating the separated cells in a selective medium, such that the stem cells are selectively expanded.
WO 93/18136 describes a process for in vitro support of mammalian cells derived from peripheral blood.
WO 93/18648 relates to a composition comprising human neutrophil precursor cells with a high content of myeloblasts and promyelocytes for treating genetic or acquired neutropenia.
WO 94/08039 describes a method of enrichment for human hematopoietic stem cells by selection for cells which express c-kit protein.
WO 94/11493 describes a stem cell population that are CD34+ and small in size, which are isolated using a counterflow elutriation method.
WO 94/27698 relates to a method combining immunoaffinity separation and continuous flow centrifugal separation for the selective separation of a nucleated heterogeneous cell population from a heterogeneous cell mixture.
WO 94/25848 describes a cell separation apparatus for collection and manipulation of target cells.
The long term culturing of highly enriched CD34+ precursors of hematopoietic progenitor cells from human bone marrow in cultures containing IL-1a, IL-3, IL-6 or GM-CSF is discussed in Brandt et al J. Clin. Invest. 86: 932-941, 1990).
One aspect of the present invention provides a method for selective ex-vivo expansion of stem cells. The term "stem cell" refers to the totipotent hematopoietic stem cells as well as early precursors and progenitor cells which can be isolated from bone marrow, spleen or peripheral blood. The term "expansion" refers to the differentiation and proliferation of the cells. The present invention provides a method for selective ex-vivo expansion of stem cells, comprising the steps of: (a) separating stem cells from other cells, (b) culturing said separated stem cells with a selective media which contains multi-functional hematopoietic receptor agonist protein(s) and (c) harvesting said stems cells. Stem cells, as well as committed progenitor cells destined to become neutrophils, erythrocytes, platelets, etc. may be distinguished from most other cells by the presence or absence of particular progenitor marker antigens, such as D34, that are present on the surface of these cells nd/or by morphological characteristics. The phenotype for a highly enriched human stem cell fraction is reported as CD34+, Thy-1+ and lin-, but it is to be understood that the present invention is not limited to the expansion of this stem cell population. The CD34+ enriched human stem cell fraction can be separated by a number of reported methods, including affinity columns or beads, magnetic beads or flow cytometry using antibodies directed to surface antigens such as the CD34+. Further, physical separation methods such as counterflow elutriation may be used to enrich hematopoietic progenitors. The CD34+ progenitors are heterogeneous, and may be divided into several sub-populations characterized by the presence or absence of co-expression of different lineage associated cell surface associated molecules. The most immature progenitor cells do not express any known lineage associated markers, such as HLA-DR or CD38, but they may express CD90(thy-1). Other surface antigens such as CD33, CD38, CD41, CD71, HLA-DR or c-kit can also be used to selectively isolate hematopoietic progenitors. The separated cells can be incubated in selected medium in a culture flask, sterile bag or in hollow fibers. Various colony stimulating factors may be utilized in order to selectively expand cells. Representative factors that have been utilized for ex-vivo expansion of bone marrow include, c-kit ligand, IL-3, G-CSF, GM-CSF, IL-1, IL-6, IL-11, flt-3 ligand or combinations thereof. The proliferation of the stem cells can be monitored by enumerating the number of stem cells and other cells, by standard techniques (e.g. hemacytometer, CFU, LTCIC) or by flow cytometry prior and subsequent to incubation.
Several methods for ex-vivo expansion of stem cells have been reported utilizing a number of selection methods and expansion using various colony stimulating factors including c-kit ligand (Brandt et al., Blood 83: 1507-1514 [1994], McKenna et al., Blood 86: 3413-3420 [1995]), IL-3 (Brandt et al., Blood 83: 1507-1514 [1994], Sato et al., Blood 82: 3600-3609 [1993]), G-CSF (Sato et al., Blood 82: 3600-3609 [1993]), GM-CSF (Sato et al., Blood 82: 3600-3609 [1993]), IL-1 (Muench et al., Blood 81: 3463-3473 [1993]), IL-6 (Sato et al., Blood 82: 3600-3609 [1993]), IL-11 (Lemoli et al., Exp. Hem. 21: 1668-1672 [1993], Sato et al., Blood 82: 3600-3609 [1993]), flt-3 ligand (McKenna et al., Blood 86: 3413 3420 [1995]) and/or combinations thereof (Brandt et al., Blood 83: 1507 1514 [1994], Haylock et al., Blood 80: 1405-1412 [1992], Koller et al., Biotechnology 11: 358-363 [1993], (Lemoli et al., Exp. Hem. 21: 1668-1672 [1993]), McKenna et al., Blood 86: 3413-3420 [1995], Muench et al., Blood 81: 3463-3473 [1993], Patchen et al., Biotherapy 7: 13-26 [1994], Sato et al., Blood 82: 3600-3609 [1993], Smith et al., Exp. Hem. 21: 870-877 [1993], Steen et al., Stem Cells 12: 214-224 [1994], Tsujino et al., Exp. Hem. 21: 1379-1386 [1993]). Among the individual colony stimulating factors, hIL-3 has been shown to be one of the most potent in expanding peripheral blood CD34+ cells (Sato et al., Blood 82: 3600-3609 [1993], Kobayashi et al., Blood 73: 1836-1841 [1989]). However, no single factor has been shown to be as effective as the combination of multiple factors. The present invention provides methods for ex vivo expansion that utilize multi-functional hematopoietic receptor agonists that are more effective than a single factor alone.
Another aspect of the invention provides methods of sustaining and/or expanding hematopoietic precursor cells which includes inoculating the cells into a culture vessel which contains a culture medium that has been conditioned by exposure to a stromal cell line such as HS-5 (WO 96/02662, Roecklein and Torok-Strob, Blood 85: 997-1105, 1995) that has been supplemented with a multi-functional hematopoietic receptor agonist of the present invention.
Another projected clinical use of growth factors has been in the in vitro activation of hematopoietic progenitors and stem cells for gene therapy. Due to the long life-span of hematopoietic progenitor cells and the distribution of their daughter cells throughout the entire body, hematopoietic progenitor cells are good candidates for ex vivo gene transfection. In order to have the gene of interest incorporated into the genome of the hematopoietic progenitor or stem cell one needs to stimulate cell division and DNA replication. Hematopoietic stem cells cycle at a very low frequency which means that growth factors may be useful to promote gene transduction and thereby enhance the clinical prospects for gene therapy. Potential applications of gene therapy (review Crystal, Science 270: 404-410 [1995]) include; 1) the treatment of many congenital metabolic disorders and immunodeficiencies (Kay and Woo, Trends Genet. 10: 253-257 [1994]), 2) neurological disorders (Friedmann, Trends Genet. 10: 210-214 [1994]), 3) cancer (Culver and Blaese, Trends Genet. 10: 174-178 [1994]) and 4) infectious diseases (Gilboa and Smith, Trends Genet. 10: 139-144 [1994]).
There are a variety of methods, known to those with skill in the art, for introducing genetic material into a host cell. A number of vectors, both viral and non-viral have been developed for transferring therapeutic genes into primary cells. Viral based vectors include; 1) replication deficient recombinant retrovirus (Boris-Lawrie and Temin, Curr. Opin. Genet. Dev. 3: 102-109 [1993], Boris-Lawrie and Temin, Annal. New York Acad. Sci. 716: 59-71 [1994], Miller, Current Top. Microbiol. Immunol. 158: 1-24 [1992]) and replication-deficient recombinant adenovirus (Berkner, BioTechniques 6: 616-629 [1988], Berkner, Current Top. Microbiol. Immunol. 158: 39-66 [1992], Brody and Crystal, Annal. New York Acad. Sci. 716: 90-103 [1994]). Non-viral based vectors include protein/DNA complexes (Cristiano et al., PNAS USA. 90: 2122-2126 [1993], Curiel et al., PNAS USA 88: 8850-8854 [1991], Curiel, Annal. New York Acad. Sci. 716: 36-58 [1994]), electroporation and liposome mediated delivery such as cationic liposomes (Farhood et al., Annal. New York Acad. Sci. 716: 23-35 [1994]).
The present invention provides an improvement to the existing methods of expanding hematopoietic cells, which new genetic material has been introduced, in that it provides methods utilizing multi-functional hematopoietic receptor agonist proteins that have improved biological activity, including an activity not seen by any single colony stimulation factor.
Many drugs may cause bone marrow suppression or hematopoietic deficiencies. Examples of such drugs are AZT, DDI, alkylating agents and anti-metabolites used in chemotherapy, antibiotics such as chloramphenicol, penicillin, gancyclovir, daunomycin and sulfa drugs, phenothiazones, tranquilizers such as meprobamate, analgesics such as aminopyrine and dipyrone, anti-convulsants such as phenytoin or carbamazepine, antithyroids such as propylthiouracil and methimazole and diuretics. The multi-functional hematopoietic receptor agonists of the present invention may be useful in preventing or treating the bone marrow suppression or hematopoietic deficiencies which often occur in patients treated with these drugs.
Hematopoietic deficiencies may also occur as a result of viral, microbial or parasitic infections and as a result of treatment for renal disease or renal failure, e.g., dialysis. The multi-functional hematopoietic receptor agonists of the present invention may be useful in treating such hematopoietic deficiencies.
The treatment of hematopoietic deficiency may include administration of a pharmaceutical composition containing the multi-functional hematopoietic receptor agonists to a patient. The multi-functional hematopoietic receptor agonists of the present invention may also be useful for the activation and amplification of hematopoietic precursor cells by treating these cells in vitro with the multi-functional hematopoietic receptor agonist proteins of the present invention prior to injecting the cells into a patient.
Various immunodeficiencies, e.g., in T and/or B lymphocytes, or immune disorders, e.g., rheumatoid arthritis, may also be beneficially affected by treatment with the multi-functional hematopoietic receptor agonists of the present invention. Immunodeficiencies may be the result of viral infections, e.g., HTLVI, HTLVII, HTLVIII, severe exposure to radiation, cancer therapy or the result of other medical treatment. The multi-functional hematopoietic receptor agonists of the present invention may also be employed, alone or in combination with other colony stimulating factors, in the treatment of other blood cell deficiencies, including thrombocytopenia (platelet deficiency), or anemia. Other uses for these novel polypeptides are the in vivo and ex vivo treatment of patients recovering from bone marrow transplants, and in the development of monoclonal and polyclonal antibodies generated by standard methods for diagnostic or therapeutic use.
Other aspects of the present invention are methods and therapeutic compositions for treating the conditions referred to above. Such compositions comprise a therapeutically effective amount of one or more of the multi-functional hematopoietic receptor agonists of the present invention in a mixture with a pharmaceutically acceptable carrier. This composition can be administered either parenterally, intravenously or subcutaneously. When administered, the therapeutic composition for use in this invention is preferably in the form of a pyrogen-free, parenterally acceptable aqueous solution. The preparation of such a parenterally acceptable protein solution, having due regard to pH, isotonicity, stability and the like, is within the skill of the art.
The dosage regimen involved in a method for treating the above-described conditions will be determined by the attending physician considering various factors which modify the action of drugs, e.g., the condition, body weight, sex and diet of the patient, the severity of any infection, time of administration and other clinical factors. Generally, a daily regimen may be in the range of 0.2-150 μg/kg of multi-functional hematopoietic receptor agonist protein per kilogram of body weight. Dosages would be adjusted relative to the activity of a given multi-functional hematopoietic receptor agonist protein and it would not be unreasonable to note that dosage regimens may include doses as low as 0.1 microgram and as high as 1 milligram per kilogram of body weight per day. In addition, there may exist specific circumstances where dosages of multi-functional hematopoietic receptor agonist would be adjusted higher or lower than the range of 0.2-150 micrograms per kilogram of body weight. These include co-administration with other colony stimulating factors or IL-3 variants or growth factors; co-administration with chemotherapeutic drugs and/or radiation; the use of glycosylated multi-functional hematopoietic receptor agonist protein; and various patient-related issues mentioned earlier in this section. As indicated above, the therapeutic method and compositions may also include co-administration with other human factors. A non-exclusive list of other appropriate colony stimulating factors (CSFs), cytokines, lymphokines, hematopoietic growth factors and interleukins for simultaneous or serial co-administration with the polypeptides of the present invention includes GM-CSF, G-CSF, c-mpl ligand (also known as TPO or MGDF), M-CSF, erythropoietin (EPO), IL-1, IL-4, IL-2, IL-3, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-15, IL-16, LIF, flt3 ligand, and eosinophil differentiation factor, stem cell factor (SCF) also known as steel factor or c-kit ligand, or combinations thereof. The dosage recited above would be adjusted to compensate for such additional components in the therapeutic composition. Progress of the treated patient can be monitored by periodic assessment of the hematological profile, e.g., differential cell count and the like.
Materials and Methods
Unless noted otherwise, all specialty chemicals were obtained from Sigma, Co. (St. Louis, Mo.). Restriction endonucleases and T4 DNA ligase were obtained from New England Biolabs (Beverly, Mass.) or Boehringer Mannheim (Indianapolis, Ind.).
Transformation of E. coli strains
E. coli strains, such as DH5α™ (Life Technologies, Gaithersburg, Md.) and TG1 (Amersham Corp., Arlington Heights, Ill.) are used for transformation of ligation reactions and are the source of plasmid DNA for transfecting mammalian cells. E. coli strains, such as JM101 (Yanisch-Perron, et al., Gene, 33: 103-119, 1985) and MON105 (Obukowicz, et al., Appl. and Envir. Micr., 58: 1511-1523, 1992) can be used for expressing the multi-functional hematopoietic receptor agonist of the present invention in the cytoplasm or periplasmic space.
MON105 ATCC#55204: F-, lambda-,IN(rrnD, rrE)1, rpoD+, rpoH358
DH5α™: F-, phi80dlacZdeltaM15, delta(lacZYA-argF)U169, deoR, recA1, endA1, hsdR17(rk-,mk+), phoA, supE44lamda-, thi-1, gyrA96, relA1
TG1: delta(lac-pro), supE, thi-1, hsdD5/F'(traD36, proA+B+,
lacIq, lacZdeltaM15)
JM101 ATCC#33876: delta (pro lac), supE, thi, F'(traD36, proA+B+, lacIq, lacZdeltaM15)
DH5α™ Subcloning efficiency cells are purchased as competent cells and are ready for transformation using the manufacturer's protocol, while both E. coli strains TG1 and MON105 are rendered competent to take up DNA using a CaCl2 method. Typically, 20 to 50 mL of cells are grown in LB medium (1% bacto-tryptone, 0.5% bacto-yeast extract, 150 mM NaCl) to a density of approximately 1.0 optical density unit at 600 nanometers (OD600) as measured by a Baush & Lomb Spectronic spectrophotometer (Rochester, N.Y.). The cells are collected by centrifugation and resuspended in one-fifth culture volume of CaCl2 solution (50 mM CaCl2, 10 mM Tris-Cl, pH7.4) and are held at 4° C. for 30 minutes. The cells are again collected by centrifugation and resuspended in one-tenth culture volume of CaCl2 solution. Ligated DNA is added to 0.2 mL of these cells, and the samples are held at 4° C. for 30-60 minutes. The samples are shifted to 42° C. for two minutes and 1.0 mL of LB is added prior to shaking the samples at 37° C. for one hour. Cells from these samples are spread on plates (LB medium plus 1.5% bacto-agar) containing either ampicillin (100 micrograms/mL, ug/mL) when selecting for ampicillin-resistant transformants, or spectinomycin (75 ug/mL) when selecting for spectinomycin-resistant transformants. The plates are incubated overnight at 37° C. Colonies are picked and inoculated into LB plus appropriate antibiotic (100 ug/mL ampicillin or 75 ug/mL spectinomycin) and are grown at 37° C. while shaking.
Methods for creation of genes with new N-terminus/C-terminus
Method I. Creation of genes with new N-terminus/C-terminus which contain a linker region (L2).
Genes with new N-terminus/C-terminus which contain a linker region (L2) separating the original C-terminus and N-terminus can be made essentially following the method described in L. S. Mullins, et al J. Am. Chem. Soc. 116, 5529-5533, 1994). Multiple steps of polymerase chain reaction (PCR) amplifications are used to rearrange the DNA sequence encoding the primary amino acid sequence of the protein. The steps are illustrated in FIG. 2.
In the first step, the first primer set ("new start" and "linker start") is used to create and amplify, from the original gene sequence, the DNA fragment ("Fragment Start") that contains the sequence encoding the new N-terminal portion of the new protein followed by the linker (L2) that connects the C-terminal and N-terminal ends of the original protein. In the second step, the second primer set ("new stop" and "linker stop") is used to create and amplify, from the original gene sequence, the DNA fragment ("Fragment Stop") that encodes the same linker as used above, followed by the new C-terminal portion of the new protein. The "new start" and "new stop" primers are designed to include the appropriate restriction sites which allow cloning of the new gene into expression plasmids. Typical PCR conditions are one cycle 95° C. melting for two minutes; 25 cycles 94° C. denaturation for one minute, 50° C. annealing for one minute and 72° C. extension for one minute; plus one cycle 72° C. extension for seven minutes. A Perkin Elmer GeneAmp PCR Core Reagents kit is used. A 100 ul reaction contains 100 pmole of each primer and one ug of template DNA; and 1× PCR buffer, 200 uM dGTP, 200 uM DATP, 200 uM dTTP, 200 uM dCTP, 2.5 units AmpliTaq DNA polymerase and 2 mM MgCl2. PCR reactions are performed in a Model 480 DNA thermal cycler (Perkin Elmer Corporation, Norwalk, Conn.).
"Fragment Start" and "Fragment Stop", which have complementary sequence in the linker region and the coding sequence for the two amino acids on both sides of the linker, are joined together in a third PCR step to make the full-length gene encoding the new protein. The DNA fragments "Fragment Start" and "Fragment Stop" are resolved on a 1% TAE gel, stained with ethidium bromide and isolated using a Qiaex Gel Extraction kit (Qiagen). These fragments are combined in equimolar quantities, heated at 70° C. for ten minutes and slow cooled to allow annealing through their shared sequence in "linker start" and "linker stop". In the third PCR step, primers "new start" and "new stop" are added to the annealed fragments to create and amplify the full-length new N-terminus/C-terminus gene. Typical PCR conditions are one cycle 95° C. melting for two minutes; 25 cycles 94° C. denaturation for one minute, 60° C. annealing for one minute and 72° C. extension for one minute; plus one cycle 72° C. extension for seven minutes. A Perkin Elmer GeneAmp PCR Core Reagents kit is used. A 100 ul reaction contains 100 pmole of each primer and approximately 0.5 ug of DNA; and 1× PCR buffer, 200 uM dGTP, 200 uM dATP, 200 uM dTTP, 200 uM dCTP, 2.5 units AmpliTaq DNA polymerase and 2 mM MgCl2. PCR reactions are purified using a Wizard PCR Preps kit (Promega).
Method II. Creation of genes with new N-terminus/C-terminus without a linker region.
New N-terminus/C-terminus genes without a linker joining the original N-terminus and C-terminus can be made using two steps of PCR amplification and a blunt end ligation. The steps are illustrated in FIG. 3. In the first step, the primer set ("new start" and "P-bl start") is used to create and amplify, from the original gene sequence, the DNA fragment ("Fragment Start") that contains the sequence encoding the new N-terminal portion of the new protein. In the second step, the primer set ("new stop" and "P-bl stop") is used to create and amplify, from gene sequence, the DNA fragment ("Fragment Stop") that contains the sequence encoding the new C-terminal portion of the new protein. The "new start" and "new stop" primers are designed to include appropriate restriction sites which allow cloning of the new gene into expression vectors. Typical PCR conditions are one cycle 95° C. melting for two minutes; 25 cycles 94° C. denaturation for one minute, 50° C. annealing for 45 seconds and 72° C. extension for 45 seconds. Deep Vent polymerase (New England Biolabs) is used to reduce the occurrence of overhangs in conditions recommended by the manufacturer. The "P-bl start" and "P-bl stop" primers are phosphorylated at the 5' end to aid in the subsequent blunt end ligation of "Fragment Start" and "Fragment Stop" to each other. A 100 ul reaction contained 150 pmole of each primer and one ug of template DNA; and 1× Vent buffer (New England Biolabs), 300 uM dGTP, 300 uM DATP, 300 uM dTTP, 300 uM dCTP, and 1 unit Deep Vent polymerase. PCR reactions are performed in a Model 480 DNA thermal cycler (Perkin Elmer Corporation, Norwalk, Conn.). PCR reaction products are purified using a Wizard PCR Preps kit (Promega).
The primers are designed to include appropriate restriction sites which allow for the cloning of the new gene into expression vectors. Typically "Fragment Start" is designed to create NcoI restriction site, and "Fragment Stop" is designed to create a HindIII restriction site. Restriction digest reactions are purified using a Magic DNA Clean-up System kit (Promega). Fragments Start and Stop are resolved on a 1% TAE gel, stained with ethidium bromide and isolated using a Qiaex Gel Extraction kit (Qiagen). These fragments are combined with and annealed to the ends of the ˜3800 base pair NcoI/HindIII vector fragment of pMON3934 by heating at 50° C. for ten minutes and allowed to slow cool. The three fragments are ligated together using T4 DNA ligase (Boehringer Mannheim). The result is a plasmid containing the full-length new N-terminus/C-terminus gene. A portion of the ligation reaction is used to transform E. coli strain DH5a cells (Life Technologies, Gaithersburg, Md.). Plasmid DNA is purified and sequence confirmed as below.
Method III. Creation of new N-terminus/C-terminus genes by tandem-duplication method
New N-terminus/C-terminus genes can be made based on the method described in R. A. Horlick, et al Protein Eng. 5: 427-431, 1992). Polymerase chain reaction (PCR) amplification of the new N-terminus/C-terminus genes is performed using a tandemly duplicated template DNA. The steps are illustrated in FIG. 3.
The tandemly-duplicated template DNA is created by cloning and contains two copies of the gene separated by DNA sequence encoding a linker connecting the original C- and N-terminal ends of the two copies of the gene. Specific primer sets are used to create and amplify a full-length new N terminus/C-terminus gene from the tandemly-duplicated template DNA. These primers are designed to include appropriate restriction sites which allow for the cloning of the new gene into expression vectors. Typical PCR conditions are one cycle 95° C. melting for two minutes; 25 cycles 94° C. denaturation for one minute, 50° C. annealing for one minute and 72° C. extension for one minute; plus one cycle 72° C. extension for seven minutes. A Perkin Elmer GeneAmp PCR Core Reagents kit (Perkin Elmer Corporation, Norwalk, Conn.) is used. A 100 ul reaction contains 100 pmole of each primer and one ug of template DNA; and 1× PCR buffer, 200 uM dGTP, 200 uM DATP, 200 uM dTTP, 200 uM dCTP, 2.5 units AmpliTaq DNA polymerase and 2 mM MgCl2. PCR reactions are performed in a Model 480 DNA thermal cycler (Perkin Elmer Corporation, Norwalk, Conn.). PCR reactions are purified using a Wizard PCR Preps kit (Promega).
Cloning of new N-terminus/C-terminus genes into multi-functional receptor agonist expression vectors
The new N-terminus/C-terminus gene is digested with restriction endonucleases to create ends that are compatible to insertion into an expression vector containing another colony stimulating factor gene. This expression vector is likewise digested with restriction endonucleases to form compatible ends. After purification, the gene and the vector DNAs are combined and ligated using T4 DNA ligase. A portion of the ligation reaction is used to transform E. coli. Plasmid DNA is purified and sequenced to confirm the correct insert. The correct clones are grown for protein expression.
DNA isolation and characterization
Plasmid DNA can be isolated by a number of different methods and using commercially available kits known to those skilled in the art. A few such methods are shown herein. Plasmid DNA is isolated using the Promega Wizard™ Miniprep kit (Madison, Wis.), the Qiagen QIAwell Plasmid isolation kits (Chatsworth, Calif.) or Qiagen Plasmid Midi kit. These kits follow the same general procedure for plasmid DNA isolation. Briefly, cells are pelleted by centrifugation (5000×g), plasmid DNA released with sequential NaOH/acid treatment, and cellular debris is removed by centrifugation (10000×g). The supernatant (containing the plasmid DNA) is loaded onto a column containing a DNA-binding resin, the column is washed, and plasmid DNA eluted with TE. After screening for the colonies with the plasmid of interest, the E. coli cells are inoculated into 50-100 mls of LB plus appropriate antibiotic for overnight growth at 37° C. in an air incubator while shaking. The purified plasmid DNA is used for DNA sequencing, further restriction enzyme digestion, additional subcloning of DNA fragments and transfection into mammalian, E. coli or other cells.
Sequence confirmation
Purified plasmid DNA is resuspended in dH2 O and quantitated by measuring the absorbance at 260/280 nm in a Bausch and Lomb Spectronic 601 UV spectrometer. DNA samples are sequenced using ABI PRISM™ DyeDeoxy™ terminator sequencing chemistry (Applied Biosystems Division of Perkin Elmer Corporation, Lincoln City, Calif.) kits (Part Number 401388 or 402078) according to the manufacturers suggested protocol usually modified by the addition of 5% DMSO to the sequencing mixture. Sequencing reactions are performed in a Model 480 DNA thermal cycler (Perkin Elmer Corporation, Norwalk, Conn.) following the recommended amplification conditions. Samples are purified to remove excess dye terminators with Centri-Sep™ spin columns (Princeton Separations, Adelphia, N.J.) and lyophilized. Fluorescent dye labeled sequencing reactions are resuspended in deionized formamide, and sequenced on denaturing 4.75% polyacrylamide-8M urea gels using an ABI Model 373A automated DNA sequencer. Overlapping DNA sequence fragments are analyzed and assembled into master DNA contigs using Sequencher v2.1 DNA analysis software (Gene Codes Corporation, Ann Arbor, Mich.).
Expression of multi-functional receptor agonists in mammalian cells
Mammalian Cell Transfection/Production of Conditioned Media
The BHK-21 cell line can be obtained from the ATCC (Rockville, Md.). The cells are cultured in Dulbecco's modified Eagle media (DMEM/high-glucose), supplemented to 2 mM (mM) L-glutamine and 10% fetal bovine serum (FBS). This formulation is designated BHK growth media. Selective media is BHK growth media supplemented with 453 units/mL hygromycin B (Calbiochem, San Diego, Calif.). The BHK-21 cell line was previously stably transfected with the HSV transactivating protein VP16, which transactivates the IE110 promoter found on the plasmid pMON3359 (See Hippenmeyer et al., Bio/Technology, pp.1037-1041, 1993). The VP16 protein drives expression of genes inserted behind the IE110 promoter. BHK-21 cells expressing the transactivating protein VP16 are designated BHK-VP16. The plasmid pMON1118 (See Highkin et al., Poultry Sci., 70: 970-981, 1991) expresses the hygromycin resistance gene from the SV40 promoter. A similar plasmid is available from ATCC, pSV2-hph.
BHK-VP16 cells are seeded into a 60 millimeter (mm) tissue culture dish at 3×105 cells per dish 24 hours prior to transfection. Cells are transfected for 16 hours in 3 mL of "OPTIMEM"™ (Gibco-BRL, Gaithersburg, Md.) containing 10 ug of plasmid DNA containing the gene of interest, 3 ug hygromycin resistance plasmid, pMON1118, and 80 ug of Gibco-BRL "LIPOFECTAMINE"™ per dish. The media is subsequently aspirated and replaced with 3 mL of growth media. At 48 hours post-transfection, media from each dish is collected and assayed for activity (transient conditioned media). The cells are removed from the dish by trypsin-EDTA, diluted 1:10 and transferred to 100 mm tissue culture dishes containing 10 mL of selective media. After approximately 7 days in selective media, resistant cells grow into colonies several millimeters in diameter. The colonies are removed from the dish with filter paper (cut to approximately the same size as the colonies and soaked in trypsin/EDTA) and transferred to individual wells of a 24 well plate containing 1 mL of selective media. After the clones are grown to confluence, the conditioned media is re-assayed, and positive clones are expanded into growth media.
Expression of multi-functional receptor agonists in E. coli
E. coli strain MON105 or JM101 harboring the plasmid of interest are grown at 37° C. in M9 plus casamino acids medium with shaking in a air incubator Model G25 from New Brunswick Scientific (Edison, N.J.). Growth is monitored at OD600 until it reaches a value of 1.0 at which time Nalidixic acid (10 milligrams/mL) in 0.1 N NaOH is added to a final concentration of 50 μg/mL. The cultures are then shaken at 37° C. for three to four additional hours. A high degree of aeration is maintained throughout culture period in order to achieve maximal production of the desired gene product. The cells are examined under a light microscope for the presence of inclusion bodies (IB). One mL aliquots of the culture are removed for analysis of protein content by boiling the pelleted cells, treating them with reducing buffer and electrophoresis via SDS-PAGE (see Maniatis et al. Molecular Cloning: A Laboratory Manual, 1982). The culture is centrifuged (5000×g) to pellet the cells.
Inclusion Body preparation, Extraction, Refolding, Dialysis, DEAE Chromatography, and Characterization of the multi-functional hematopoietic receptor agonists which accumulate as inclusion bodies in E. coli
Isolation of Inclusion Bodies
The cell pellet from a 330 mL E. coli culture is resuspended in 15 mL of sonication buffer (10 mM 2-amino-2-(hydroxymethyl) 1,3-propanediol hydrochloride (Tris-HCl), pH 8.0+1 mM ethylenediaminetetraacetic acid (EDTA). These resuspended cells are sonicated using the microtip probe of a Sonicator Cell Disruptor (Model W-375, Heat Systems-Ultrasonics, Inc., Farmingdale, N.Y.). Three rounds of sonication in sonication buffer followed by centrifugation are employed to disrupt the cells and wash the inclusion bodies (IB). The first round of sonication is a 3 minute burst followed by a 1 minute burst, and the final two rounds of sonication are for 1 minute each.
Extraction and refolding of proteins from inclusion body pellets
Following the final centrifugation step, the IB pellet is resuspended in 10 mL of 50 mM Tris-HCl, pH 9.5, 8 M urea and 5 mM dithiothreitol (DTT) and stirred at room temperature for approximately 45 minutes to allow for denaturation of the expressed protein.
The extraction solution is transferred to a beaker containing 70 mL of 5 mM Tris-HCl, pH 9.5 and 2.3 M urea and gently stirred while exposed to air at 4° C. for 18 to 48 hours to allow the proteins to refold. Refolding is monitored by analysis on a Vydac (Hesperia, Calif.) C18 reversed phase high pressure liquid chromatography (RP-HPLC) column (0.46×25 cm). A linear gradient of 40% to 65% acetonitrile, containing 0.1% trifluoroacetic acid (TFA), is employed to monitor the refold. This gradient is developed over 30 minutes at a flow rate of 1.5 mL per minute. Denatured proteins generally elute later in the gradient than the refolded proteins.
Purification
Following the refold, contaminating E. coli proteins are removed by acid precipitation. The pH of the refold solution is titrated to between pH 5.0 and pH 5.2 using 15% (v/v) acetic acid (HOAc). This solution is stirred at 4° C. for 2 hours and then centrifuged for 20 minutes at 12,000×g to pellet any insoluble protein.
The supernatant from the acid precipitation step is dialyzed using a Spectra/Por 3 membrane with a molecular weight cut off (MWCO) of 3,500 daltons. The dialysis is against 2 changes of 4 liters (a 50-fold excess) of 10 mM Tris-HCl, pH 8.0 for a total of 18 hours. Dialysis lowers the sample conductivity and removes urea prior to DEAE chromatography. The sample is then centrifuged (20 minutes at 12,000×g) to pellet any insoluble protein following dialysis.
A Bio-Rad Bio-Scale DEAE2 column (7×52 mm) is used for ion exchange chromatography. The column is equilibrated in a buffer containing 10 mM Tris-HCl, pH 8.0, and a 0-to-500 mM sodium chloride (NaCl) gradient, in equilibration buffer, over 45 column volumes is used to elute the protein. A flow rate of 1.0 mL per minute is used throughout the run. Column fractions (2.0 mL per fraction) are collected across the gradient and analyzed by RP HPLC on a Vydac (Hesperia, Calif.) C18 column (0.46×25 cm). A linear gradient of 40% to 65% acetonitrile, containing 0.1% trifluoroacetic acid (TFA), is employed. This gradient is developed over 30 minutes at a flow rate of 1.5 mL per minute. Pooled fractions are then dialyzed against 2 changes of 4 liters (50-to-500-fold excess) of 10 mM ammonium acetate (NH4Ac), pH 4.0 for a total of 18 hours. Dialysis is performed using a Spectra/Por 3 membrane with a MWCO of 3,500 daltons. Finally, the sample is sterile filtered using a 0.22 μm syringe filter (μStar LB syringe filter, Costar, Cambridge, Mass.), and stored at 4° C.
In some cases the folded proteins can be affinity purified using affinity reagents such as mAbs or receptor subunits attached to a suitable matrix. Alternatively, (or in addition) purification can be accomplished using any of a variety of chromatographic methods such as: ion exchange, gel filtration or hydrophobic chromatography or reversed phase HPLC.
These and other protein purification methods are described in detail in Methods in Enzymology, Volume 182 `Guide to Protein Purification` edited by Murray Deutscher, Academic Press, San Diego, Calif. (1990).
Protein Characterization
The purified protein is analyzed by RP-HPLC, electrospray mass spectrometry, and SDS-PAGE. The protein quantitation is done by amino acid composition, RP-HPLC, and Bradford protein determination. In some cases tryptic peptide mapping is performed in conjunction with electrospray mass spectrometry to confirm the identity of the protein.
AML Proliferation Assay for Bioactive Human Interleukin-3
The factor-dependent cell line AML 193 was obtained from the American Type Culture Collection (ATCC, Rockville, Md.). This cell line, established from a patient with acute myelogenous leukemia, is a growth factor dependent cell line which displayed enhanced growth in GM-CSF supplemented medium (Lange, B., et al., Blood 70: 192, 1987; Valtieri, M., et al., J. Immunol. 138: 4042, 1987). The ability of AML 193 cells to proliferate in the presence of human IL-3 has also been documented. (Santoli, D., et al., J. Immunol. 139: 348, 1987). A cell line variant was used, AML 193 1.3, which was adapted for long term growth in IL-3 by washing out the growth factors and starving the cytokine dependent AML 193 cells for growth factors for 24 hours. The cells are then replated at 1×105 cells/well in a 24 well plate in media containing 100 U/mL IL-3. It took approximately 2 months for the cells to grow rapidly in IL-3. These cells are maintained as AML 193 1.3 thereafter by supplementing tissue culture medium (see below) with human IL-3.
AML 193 1.3 cells are washed 6 times in cold Hanks balanced salt solution (HBSS, Gibco, Grand Island, N.Y.) by centrifuging cell suspensions at 250×g for 10 minutes followed by decantation of the supernatant. Pelleted cells are resuspended in HBSS and the procedure is repeated until six wash cycles are completed. Cells washed six times by this procedure are resuspended in tissue culture medium at a density ranging from 2×105 to 5×105 viable cells/mL. This medium is prepared by supplementing Iscove's modified Dulbecco's Medium (IMDM, Hazelton, Lenexa, Kans.) with albumin, transferrin, lipids and 2-mercaptoethanol. Bovine albumin (Boehringer-Mannheim, Indianapolis, Ind.) is added at 500 μg/mL; human transferrin (Boehringer-Mannheim, Indianapolis, Ind.) is added at 100 μg/mL; soybean lipid (Boehringer-Mannheim, Indianapolis, Ind.) is added at 50 μg/mL; and 2-mercaptoethanol (Sigma, St. Louis, Mo.) is added at 5×10-5 M.
Serial dilutions of human interleukin-3 or multi-functional hematopoietic receptor agonist proteins are made in triplicate series in tissue culture medium supplemented as stated above in 96 well Costar 3596 tissue culture plates. Each well contained 50 μl of medium containing interleukin-3 or multi-functional hematopoietic receptor agonist proteins once serial dilutions are completed. Control wells contained tissue culture medium alone (negative control). AML 193 1.3 cell suspensions prepared as above are added to each well by pipetting 50 μl (2.5×104 cells) into each well. Tissue culture plates are incubated at 37° C. with 5% CO2 in humidified air for 3 days. On day 3, 0.5 μCi 3 H-thymidine (2 Ci/mM, New England Nuclear, Boston, Mass.) is added in 50 μl of tissue culture medium. Cultures are incubated at 37° C. with 5% CO2 in humidified air for 18-24 hours. Cellular DNA is harvested onto glass filter mats (Pharmacia LKB, Gaithersburg, Md.) using a TOMTEC cell harvester (TOMTEC, Orange, Conn.) which utilized a water wash cycle followed by a 70% ethanol wash cycle. Filter mats are allowed to air dry and then placed into sample bags to which scintillation fluid (Scintiverse II, Fisher Scientific, St. Louis, Mo. or BetaPlate Scintillation Fluid, Pharmacia LKB, Gaithersburg, Md.) is added. Beta emissions of samples from individual tissue culture wells are counted in a LKB BetaPlate model 1205 scintillation counter (Pharmacia LKB, Gaithersburg, Md.) and data is expressed as counts per minute of 3 H-thymidine incorporated into cells from each tissue culture well. Activity of each human interleukin-3 preparation or multi-functional hematopoietic receptor agonist protein preparation is quantitated by measuring cell proliferation (3 H-thymidine incorporation) induced by graded concentrations of interleukin-3 or multi-functional hematopoietic receptor agonist. Typically, concentration ranges from 0.05 pM-105 pM are quantitated in these assays. Activity is determined by measuring the dose of interleukin-3 or multi-functional hematopoietic receptor agonist protein which provides 50% of maximal proliferation (EC50 =0.5×(maximum average counts per minute of 3 H-thymidine incorporated per well among triplicate cultures of all concentrations of interleukin-3 tested--background proliferation measured by 3 H-thymidine incorporation observed in triplicate cultures lacking interleukin-3). This EC50 value is also equivalent to 1 unit of bioactivity. Every assay is performed with native interleukin-3 as a reference standard so that relative activity levels could be assigned.
Typically, the multi-functional hematopoietic receptor agonist proteins were tested in a concentration range of 2000 pM to 0.06 pM titrated in serial 2 fold dilutions.
Activity for each sample was determined by the concentration which gave 50% of the maximal response by fitting a four-parameter logistic model to the data. It was observed that the upper plateau (maximal response) for the sample and the standard with which it was compared did not differ. Therefore relative potency calculation for each sample was determined from EC50 estimations for the sample and the standard as indicated above. AML 193.1.3 cells proliferate in response to hIL-3, hGM-CSF and hG-CSF. Therefore the following additional assays were performed for some samples to demonstrate that the G-CSF receptor agonist portion of the multi-functional hematopoietic receptor agonist proteins was active. The proliferation assay was performed with the multi-functional hematopoietic receptor agonist plus and minus neutralizing monoclonal antibodies to the hIL-3 receptor agonist portion. In addition, a fusion molecule with the factor Xa cleavage site was cleaved then purified and the halves of the molecule were assayed for proliferative activity. These experiments showed that both components of the multi-functional hematopoietic receptor agonist proteins were active.
TF1 c-mpl ligand dependent proliferation assay
The c-mpl ligand proliferative activity can be assayed using a subclone of the pluripotential human cell line TF1 (Kitamura et al., J. Cell Physiol 140: 323-334. [1989]). TF1 cells are maintained in h-IL3 (100 U/mL). To establish a sub-clone responsive to c-mpl ligand, cells are maintained in passage media containing 10% supernatant from BHK cells transfected with the gene expressing the 1-153 form of c-mpl ligand (pMON26448). Most of the cells die, but a subset of cells survive. After dilution cloning, a c-mpl ligand responsive clone is selected, and these cells are split into passage media to a density of 0.3×106 cells/mL the day prior to assay set-up. Passage media for these cells is the following: RPMI 1640 (Gibco), 10% FBS (Harlan, Lot #91206), 10% c-mpl ligand supernatant from transfected BHK cells, 1 mM sodium pyruvate (Gibco), 2 mM glutamine (Gibco), and 100 ug/mL penicillin-streptomycin (Gibco). The next day, cells are harvested and washed twice in RPMI or IMDM media with a final wash in the ATL, or assay media. ATL medium consists of the following: IMDM (Gibco), 500 ug/mL of bovine serum albumin, 100 ug/mL of human transferrin, 50 ug/mL soybean lipids, 4×10-8M beta-mercaptoethanol and 2 mL of A9909 (Sigma, antibiotic solution) per 1000 mL of ATL. Cells are diluted in assay media to a final density of 0.25×106 cells/mL in a 96-well low evaporation plate (Costar) to a final volume of 50 ul. Transient supernatants (conditioned media) from transfected clones are added at a volume of 50 ul as duplicate samples at a final concentration of 50% and diluted three-fold to a final dilution of 1.8%. Triplicate samples of a dose curve of IL-3 variant pMON13288 starting at 1 ng/mL and diluted using three-fold dilutions to 0.0014 ng/mL is included as a positive control. Plates are incubated at 5% CO2 and 37° C. At day six of culture, the plate is pulsed with 0.5 Ci of 3H/well (NEN) in a volume of 20 ul/well and allowed to incubate at 5% CO2 and 37° C. for four hours. The plate is harvested and counted on a Betaplate counter.
Other in vitro cell based proliferation assays
Other in vitro cell based assays, known to those skilled in the art, may also be useful to determine the activity of the multi-functional hematopoietic receptor agonists depending on the factors that comprise the molecule in a similar manner as described in the AML 193.1.3 cell proliferation assay. The following are examples of other useful assays.
TF1 proliferation assay: TF1 is a pluripotential human cell line (Kitamura et al., J. Cell Physiol 140: 323-334. [1989]) that responds to hIL-3.
32D proliferation assay: 32D is a murine IL-3 dependent cell line which does not respond to human IL-3 but does respond to human G-CSF which is not species restricted.
Baf/3 proliferation assay: Baf/3 is a murine IL-3 dependent cell line which does not respond to human IL-3 or human c-mpl ligand but does respond to human G-CSF which is not species restricted.
T1165 proliferation assay: T1165 cells are a IL-6 dependent murine cell line (Nordan et al., 1986) which respond to IL-6 and IL-11.
Human Plasma Clot meg-CSF Assay: Used to assay megakaryocyte colony formation activity (Mazur et al., 1981).
Transfected cell lines
Cell lines such as the murine Baf/3 cell line can be transfected with a colony stimulating factor receptor, such as the human G-CSF receptor or human c-mpl receptor, which the cell line does not have. These transfected cell lines can be used to determine the activity of the ligand for which the receptor has been transfected into the cell line.
One such transfected Baf/3 cell line was made by cloning the cDNA encoding c-mpl from a library made from a c-mpl responsive cell line and cloned into the multiple cloning site of the plasmid pcDNA3 (Invitrogen, San Diego Calif.). Baf/3 cells were transfected with the plasmid via electroporation. The cells were grown under G418 selection in the presence of mouse IL-3 in Wehi conditioned media. Clones were established through limited dilution.
In a similar manner the human G-CSF receptor can be transfected into the Baf/3 cell line and used to determine the bioactivity of the multi-functional hematopoietic receptor agoinsts.
Analysis of c-mpl ligand proliferative activity
Methods
1. Bone marrow proliferation assay
a. CD34+ Cell Purification
Bone marrow aspirates (15-20 mL) were obtained from normal allogeneic marrow donors after informed consent. Cells were diluted 1:3 in phosphate buffered saline (PBS, Gibco-BRL), 30 mL were layered over 15 mL Histopaque-1077 (Sigma) and centrifuged for 30 minutes at 300 RCF. The mononuclear interface layer was collected and washed in PBS. CD34+ cells were enriched from the mononuclear cell preparation using an affinity column per manufacturers instructions (CellPro, Inc, Bothell Wash.). After enrichment, the purity of CD34+ cells was 70% on average as determined by using flow cytometric analysis using anti-CD34 monoclonal antibody conjugated to fluorescein and anti-CD38 conjugated to phycoerythrin (Becton Dickinson, San Jose Calif.).
Cells were resuspended at 40,000 cells/mL in X-Vivo 10 media (Bio-Whittaker, Walkersville, Md.) and 1 mL was plated in 12-well tissue culture plates (Costar). The growth factor rhIL-3 was added at 100 ng/mL (pMON5873) was added to some wells. hIL3 variants were used at 10 ng/mL to 100 ng/mL. Conditioned media from BHK cells transfected with plasmid encoding c-mpl ligand or multi-functional hematopoietic receptor agonists were tested by addition of 100 μl of supernatant added to 1 mL cultures (approximately a 10% dilution). Cells were incubated at 37° C. for 8-14 days at 5% CO2 in a 37° C. humidified incubator.
b. Cell Harvest and Analysis
At the end of the culture period a total cell count was obtained for each condition. For fluorescence analysis and ploidy determination cells were washed in megakaryocyte buffer (MK buffer, 13.6 mM sodium citrate, 1 mM theophylline, 2.2 μm PGE1, 11 mM glucose, 3% w/v BSA, in PBS, pH 7.4,) (Tomer et al., Blood 70: 1735-1742, 1987) resuspended in 500 μl of MK buffer containing anti-CD41a FITC antibody (1:200, AMAC, Westbrook, Me.) and washed in MK buffer. For DNA analysis cells were permeablized in MK buffer containing 0.5% Tween 20 (Fisher, Fair Lawn N.J.) for 20 min. on ice followed by fixation in 0.5% Tween-20 and 1% paraformaldehyde (Fisher Chemical) for 30 minutes followed by incubation in propidium iodide (Calbiochem , La Jolla Calif.) (50 μg/mL) with RNA-ase (400 U/mL) in 55% v/v MK buffer (200 mOsm) for 1-2 hours on ice. Cells were analyzed on a FACScan or Vantage flow cytometer (Becton Dickinson, San Jose, Calif.). Green fluorescence (CD41a-FITC) was collected along with linear and log signals for red fluorescence (PI) to determine DNA ploidy. All cells were collected to determine the percent of cells that were CD41+. Data analysis was performed using software by LYSIS (Becton Dickinson, San Jose, Calif.). Percent of cells expressing the CD41 antigen was obtained from flow cytometry analysis (Percent). Absolute (Abs) number of CD41+ cells/mL was calculated by: (Abs)=(Cell Count)*(Percent)/100.
2. Megakaryocyte fibrin clot assay
CD34+ enriched population were isolated as described above. Cells were suspended at 25,000 cells/mL with or without cytokine(s) in a media consisting of a base Iscoves IMDM media supplemented with 0.3% BSA, 0.4 mg/mL apo-transferrin, 6.67 μM FeCl2, 25 μg/mL CaCl2, 25 μg/mL L-asparagine, 500 μg/mL ε-amino-n-caproic acid and penicillin/streptomycin. Prior to plating into 35 mm plates, thrombin was added (0.25 Units/mL) to initiate clot formation. Cells were incubated at 37° C. for 13 days at 5% CO2 in a 37° C. humidified incubator.
At the end of the culture period plates were fixed with methanol:acetone (1:3), air dried and stored at -200° C. until staining. A peroxidase immunocytochemistry staining procedure was used (Zymed, Histostain-SP. San Francisco, Calif.) using a cocktail of primary monoclonal antibodies consisting of anti-CD41a, CD42 and CD61. Colonies were counted after staining and classified as negative, CFU-MK (small colonies, 1-2 foci and less that approx. 25 cells), BFU-MK (large, multi-foci colonies with >25 cells) or mixed colonies (mixture of both positive and negative cells.
Methylcellulose Assay
This assay reflects the ability of colony stimulating factors to stimulate normal bone marrow cells to produce different types of hematopoietic colonies in vitro (Bradley et al., Aust. Exp Biol. Sci. 44: 287-300, 1966), Pluznik et al., J. Cell Comp. Physio 66: 319-324, 1965).
Methods
Approximately 30 mL of fresh, normal, healthy bone marrow aspirate are obtained from individuals following informed consent. Under sterile conditions samples are diluted 1:5 with a 1× PBS (#14040.059 Life Technologies, Gaithersburg, Md.) solution in a 50 mL conical tube (#25339-50 Corning, Corning Md.). Ficoll (Histopaque 1077 Sigma H-8889) is layered under the diluted sample and centrifuged, 300×g for 30 min. The mononuclear cell band is removed and washed two times in 1× PBS and once with 1% BSA PBS (CellPro Co., Bothel, Wash.). Mononuclear cells are counted and CD34+ cells are selected using the Ceprate LC (CD34) Kit (CellPro Co., Bothel, Wash.) column. This fractionation is performed since all stem and progenitor cells within the bone marrow display CD34 surface antigen.
Cultures are set up in triplicate with a final volume of 1.0 mL in a 35×10 mm petri dish (Nunc#174926). Culture medium is purchased from Terry Fox Labs. (HCC-4230 medium (Terry Fox Labs, Vancouver, B.C., Canada) and erythropoietin (Amgen, Thousand Oaks, Calif.) is added to the culture media. 3,000-10,000 CD34+ cells are added per dish. Recombinant IL-3, purified from mammalian cells or E. coli, and multi-functional hematopoietic receptor agonist proteins, in conditioned media from transfected mammalian cells or purified from conditioned media from transfected mammalian cells or E. coli, are added to give final concentrations ranging from 0.001 nM to 10 nM. Recombinant hIL-3, GM-CSF, c-mpl ligand and multi-functional hematopoietic receptor agonist are supplied in house. G-CSF (Neupogen) is from Amgen (Thousand Oaks Calf.). Cultures are resuspended using a 3 cc syringe and 1.0 mL is dispensed per dish. Control (baseline response) cultures received no colony stimulating factors. Positive control cultures received conditioned media (PHA stimulated human cells: Terry Fox Lab. H2400). Cultures are incubated at 37° C., 5% CO2 in humidified air. Hematopoietic colonies which are defined as greater than 50 cells are counted on the day of peak response (days 10-11) using a Nikon inverted phase microscope with a 40× objective combination. Groups of cells containing fewer than 50 cells are referred to as clusters. Alternatively colonies can be identified by spreading the colonies on a slide and stained or they can be picked, resuspended and spun onto cytospin slides for staining.
Human Cord Blood Hemopoietic Growth Factor Assays
Bone marrow cells are traditionally used for in vitro assays of hematopoietic colony stimulating factor (CSF) activity. However, human bone marrow is not always available, and there is considerable variability between donors. Umbilical cord blood is comparable to bone marrow as a source of hematopoietic stem cells and progenitors (Broxmeyer et al., PNAS USA 89: 4109-113, 1992; Mayani et al., Blood 81: 3252-3258, 1993). In contrast to bone marrow, cord blood is more readily available on a regular basis. There is also a potential to reduce assay variability by pooling cells obtained fresh from several donors, or to create a bank of cryopreserved cells for this purpose. By modifying the culture conditions, and/or analyzing for lineage specific markers, it is be possible to assay specifically for granulocyte/macrophage colonies (CFU-GM), for megakaryocyte CSF activity, or for high proliferative potential colony forming cell (HPP-CFC) activity.
Methods
Mononuclear cells (MNC) are isolated from cord blood within 24 hr. of collection, using a standard density gradient (1.077 g/mL Histopaque). Cord blood MNC have been further enriched for stem cells and progenitors by several procedures, including immunomagnetic selection for CD14-, CD34+ cells; panning for SBA-, CD34+ fraction using coated flasks from Applied Immune Science (Santa Clara, Calif.); and CD34+ selection using a CellPro (Bothell, Wash.) avidin column. Either freshly isolated or cryopreserved CD34+ cell enriched fractions are used for the assay. Duplicate cultures for each serial dilution of sample (concentration range from 1 pM to 1204 pM) are #prepared with 1×104 cells in 1 ml of 0.9% methycellulose containing medium without additional growth factors (Methocult H4230 from Stem Cell Technologies, Vancouver, BC.). In some experiments, Methocult H4330 containing erythropoietin (EPO) was used instead of Methocult H4230, or Stem Cell Factor (SCF), 50 ng/mL (Biosource International, Camarillo, Calif.) was added. After culturing for 7-9 days, colonies containing >30 cells are counted. In order to rule out subjective bias in scoring, assays are scored blind.
Additional details about recombinant DNA methods which may be used to create the variants, express them in bacteria, mammalian cells or insect cells, purification and refold of the desired proteins and assays for determining the bioactivity of the proteins may be found in co-filed Applications WO 95/00646, WO 94/12639, WO 94/12638, WO 95/20976, WO 95/21197, WO 95/20977, WO 95/21254 and US 08/383,035 which are hereby incorporated by reference in their entirety.
Further details known to those skilled in the art may be found in T. Maniatis, et al., Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory, 1982) and references cited therein, incorporated herein by reference; and in J. Sambrook, et al., Molecular Cloning, A Laboratory Manual, 2nd edition, Cold Spring Harbor Laboratory, 1989) and references cited therein, incorporated herein by reference.
                                  TABLE 1                                 
__________________________________________________________________________
OLIGONUCLEOTIDES                                                          
__________________________________________________________________________
c-mplNcoI                                                                 
      ACGTCCATGGCNTCNCCNGCNCCNCCTGCTTGTGCACTCCGAGTC                       
      (SEQ ID NO:13)                                                      
N = A, C, G or T                                                          
Ecompl  ATGCACGAATTCCCTGACGCAGAGGGTGGA                                    
                             (SEQ ID NO:14)                               
c-mplHindIII                                                              
               TGACAAGCTTACCTGACGCAGAGGGTGGACCCT                          
                             (SEQ ID NO:15)                               
4L-5'          AATTCGGCAA (SEQ ID NO:16)                                  
4L-3'          CATGTTGCCG (SEQ ID NO:17)                                  
5L-5'          AATTCGGCGGCAA (SEQ ID NO:18)                               
5L-3'          CATGTTGCCGCCG (SEQ ID NO:19)                               
8L-5'          AATTCGGCGGCAACGGCGGCAA (SEQ ID NO:20)                      
8L-3'          CATGTTGCCGCCGTTGCCGCCG  (SEQ TDNO:21)                      
31-5'          CGATCCATGGAGGTTCACCCTTTGCCT (SEQ ID NO:22)                 
31-3'          GATCAAGCTTATGGGCACTGGCTCAGTCT (SEQ ID NO:23)               
35-5'          CGATACATGTTGCCTACACCTGTCCTG (SEQ ID NO:24)                 
35-3'          GATCAAGCTTAAGGGTGAACCTCTGGGCA (SEQ ID NO:25)               
39-5'          CGATCCATGGTCCTGCTGCCTGCTGTG (SEQ ID NO:26)                 
39-3'          GATCAAGCTTAAGGTGTAGGCAAAGGGTG (SEQ ID NO:27)               
43-5'          CGATCCATGGCTGTGGACTTTAGCTTGGGA (SEQ ID NO:28)              
43-3'          GATCAAGCTTAAGGCAGCAGGACAGGTGT (SEQ ID NO:29)               
45-5'          CGATCCATGGACTTTAGCTTGGGAGAA (SEQ ID NO:30)                 
45-3'          GATCAAGCTTACACAGCAGGCAGCAGGAC (SEQ ID NO:31)               
49-5'          CGATCCATGGGAGAATGGAAAACCCAG (SEQ ID NO:32)                 
49-3'          GATCAAGCTTACAAGCTAAAGTCCACAGC (SEQ ID NO:33)               
82-5'          CGATCCATGGGACCCACTTGCCTCTCA (SEQ ID NO:34)                 
82-3'          GATCAAGCTTACAGTTGTCCCCGTGCTGC (SEQ ID NO:35)               
109-5'        CAGTCCATGGGAACCCAGCTTCCTCCA (SEQ ID NO: 36)                 
109-3'        GATCAAGCTTAAAGGAGGCTCTGCAGGGC (SEQ ID NO:37)                
116-5'        CGATCCATGGGCAGGACCACAGCTCAC (SEQ ID NO:38)                  
116-3'        GATCAAGCTTACTGTGGAGGAAGCTGGGTT (SEQ ID NO: 39)              
120-5'        CGATCCATGGCTCACAAGGATCCCAATGCC (SEQ ID NO:40)               
120-3'        GATCAAGCTTATGTGGTCCTGCCCTGTGG (SEQ ID NO:41)                
123-5'        CGATCCATGGATCCCAATGCCATCTTCCTG (SEQ ID NO:42)               
123-3'        GATCAAGCTTACTTGTGAGCTGTGGTCCT (SEQ ID NO:43)                
126-5'        CGATCCATGGCCATCTTCCTGAGCTTCCAA                              
                   (SEQ ID NO:44)                                         
126-3'        GATCAAGCTTAATTGGGATCCTTGTGAGCTGT                            
                      (SEQ ID NO:45)                                      
SYNNOXA1.REQ                                                              
              AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA                 
                            GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC   
                            TCC (SEQ ID NO:46)                            
SYNNOXA2.REQ                                                              
             CCGGGGAGCC TCCACCGCCC TCTACGTACT GTTGAGCCTG                  
                           CGCGTTCTCC AAGGTTTTCA GATAGAAGGT CAGTTTACGA    
                           CGG (SEQ ID NO:47)                             
L1syn.for                                                                 
                GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT               
                           CTAACTGCTC TATAATGAT (SEQ ID NO:48)            
L1syn.rev                                                                 
                CGATCATTAT AGAGCAGTTA GAGCCACCAC CCTGTTGTTC               
                           CTGCGCTTGC TCAAGG (SEQ ID NO:49)               
L3syn.for                                                                 
                GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT               
                           CTGGCGGTGG CAGCGGCGGC GGTTCTAACT GCTCTATAAT    
                           GAT (SEQ ID NO:50)                             
L3syn.rev                                                                 
               CGATCATTAT AGAGCAGTTA GAACCGCCGC CGCTGCCACC                
                          GCCAGAGCCA CCACCCTGTT GTTCCTGCGC TTGCTCAAGG     
                          (SEQ ID NO:51)                                  
35start.seq                                                               
              GATCGACCAT GGCTCTGGAC CCGAACAACC TC                         
                           (SEQ ID NO:52)                                 
34rev.seq                                                                 
                CTCGATTACG TACAAAGGTG CAGGTGGT                            
                           (SEQ ID NO:53)                                 
70start.seq                                                               
              GATCGACCAT GGCTAATGCA TCAGGTATTG AG                         
                           (SEQ ID NO:54)                                 
69rev.seq                                                                 
                CTCGATTACG TATTCTAAGT TCTTGACA (SEQ ID NO:55)             
91start.seq                                                               
              GATCGACCAT GGCTGCACCC TCTCGACATC CA                         
                           (SEQ ID NO:56)                                 
90rev.seq                                                                 
                CTCGATTACG TAGGCCGTGG CAGAGGGC (SEQ ID NO:57)             
101start.seq                                                              
             GATCGACCAT GGCTGCAGGT GACTGGCAAG AA                          
                           (SEQ ID NO:58)                                 
100rev.seq                                                                
               CTCGATTACG TACTTGATGA TGATTGGA (SEQ ID NO:59)              
L-11start.seq                                                             
           GCTCTGAGAG CCGCCAGAGC CGCCAGAGGG                               
                           CTGCGCAAGG TGGCGTAGAA CGCG (SEQ ID NO:60)      
L-11stop.seq                                                              
             CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG                             
                           AGCTTCCTGC TCAAGTCTTT AGAG (SEQ ID NO:61)      
P-b1start.seq                                                             
            GGGCTGCGCA AGGTGGCG (SEQ ID NO:62)                            
P-b1stop.seq                                                              
             ACACCATTGG GCCCTGCCAG C (SEQ ID NO:63)                       
39start.seq                                                               
              GATCGACCAT GGCTTACAAG CTGTGCCACC CC                         
                           (SEQ ID NO:64)                                 
38stop.Seq                                                                
               CGATCGAAGC TTATTAGGTG GCACACAGCT TCTCCT                    
                           (SEQ ID NO:65)                                 
97start.seq                                                               
              GATCGACCAT GGCTCCCGAG TTGGGTCCCA CC                         
                           (SEQ ID NO:66)                                 
96stop.Seq                                                                
               CGATCGAAGC TTATTAGGAT ATCCCTTCCA GGGCCT                    
                           (SEQ ID NO:67)                                 
126start.seq                                                              
             GATCGACCAT GGCTATGGCC CCTGCCCTGC AG                          
                           (SEQ ID NO:68)                                 
125stop.Seq                                                               
              CGATCGAAGC TTATTATCCC AGTTCTTCCA TCTGCT                     
                           (SEQ ID NO:69)                                 
133start.seq                                                              
             GATCGACCAT GGCTACCCAG GGTGCCATGC CG                          
                           (SEQ ID NO:70)                                 
132stop.seq                                                               
              CGATCGAAGC TTATTAGGGC TGCAGGGCAG GGGCCA                     
                           (SEQ ID NO:71)                                 
142start.seq                                                              
             GATCGACCAT GGCTTCTGCT TTCCAGCGCC GG                          
                           (SEQ ID NO:72)                                 
141stop.Seq                                                               
              CGATCGAAGC TTATTAGGCG AAGGCCGGCA TGGCAC                     
                           (SEQ ID NO:73)                                 
GLYXA1             GTAGAGGGCG GTGGAGGCTC C (SEQ ID NO:74)                 
GLYXA2             CCGGGGAGCC TCCACCGCCC TCTAC (SEQ ID NO:75)             
1GGGSfor                                                                  
                 TTCTACGCCA CCTTGCGCAG CCCGGCGGCG GCTCTGACAT              
                           GTCTACACCA TTG (SEQ ID NO:76)                  
1GGGSrev                                                                  
                 CAATGGTGTA GACATGTCAG AGCCGCCGCC GGGCTGCGCA              
                           AGGTGGCGTA GAA (SEQ ID NO:77)                  
Synnoxa1.req                                                              
             AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA                  
                           GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC    
                           TCC (SEQ ID NO:240)                            
Synnoxa2.req                                                              
             CCGGGGAGCC TCCACCGCCC TCTACGTACT GTTGAGCCTG                  
                           CGCGTTCTCC AAGGTTTTCA GATAGAAGGT CAGTTTACGA    
                           CGG (SEQ ID NO:241)                            
__________________________________________________________________________

                                  TABLE 2                                 
__________________________________________________________________________
GENE SEQUENCES                                                            
__________________________________________________________________________
pMON30304                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGT (SEQ ID NO:78)                      
pMON26458                                                                 
TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTC       
ACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGA       
CTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTG       
ACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCC       
TGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCT       
TCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTG       
CTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTC           
(SEQ ID NO:79)                                                            
pMON28548                                                                 
TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTC       
ACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGA       
CTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTG       
ACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCC       
TGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCT       
TCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTG       
CTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCG       
GCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTC       
CCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTG       
CCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTC       
TGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCT       
CTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT       
GGAACCCAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGC       
TCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG                  
(SEQ ID NO:80)                                                            
pMON28500                                                                 
TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTC       
ACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGA       
CTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTG       
ACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCC       
TGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCT       
TCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTG       
CTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCA       
ACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCA       
TGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCT       
GCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGG       
GAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTC       
ATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGA       
ACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCC       
AACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG         
(SEQ ID NO:81)                                                            
pMON28501                                                                 
TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTC       
ACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGA       
CTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTG       
ACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCC       
TGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCT       
TCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTG       
CTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCG       
GCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTC       
CCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTG       
CCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTC       
TGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCT       
CTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT       
GGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCT       
TCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAG       
G (SEQ ID NO:82)                                                          
pMON28502                                                                 
TCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTC       
ACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGA       
CTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTG       
ACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCC       
TGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCT       
TCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTG       
CTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCG       
GCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCT       
TCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCT       
GTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCAC       
AGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACC       
CACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAG       
AGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCT       
TCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCT       
CTGCGTCAGG (SEQ ID NO:83)                                                 
Syntan1                                                                   
1  CATGGCTAAC TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA                 
51  GACCACCTGC ACCTTTGCTG GACCCGAACA ACCTCAATGA CGAAGACGTC                
101                                                                       
    TCTATCCTGA TGGACCGAAA CCTTCGACTT CCAAACCTGG AGAGCTTCGT                
151                                                                       
    AAGGGCTGTC AAGAACTTAG AAAATGCATC AGGTATTGAG GCAATTCTTC                
201                                                                       
    GTAATCTCCA ACCATGTCTG CCCTCTGCCA CGGCCGCACC CTCTCGACAT                
251                                                                       
    CCAATCATCA TCAAGGCAGG TGACTGGCAA GAATTCCGGG AAAAACTGAC                
301                                                                       
    GTTCTATCTG GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT                
351                                                                       
    CTAACTGCTC TATAATGATC GATGAAATTA TACATCACTT AAAGAGACCA                
401                                                                       
    CCTGCACCTT TGCTGGACCC GAACAACCTC AATGACGAAG ACGTCTCTAT                
451                                                                       
    CCTGATGGAC CGAAACCTTC GACTTCCAAA CCTGGAGAGC TTCGTAAGGG                
501                                                                       
    CTGTCAAGAA CTTAGAAAAT GCATCAGGTA TTGAGGCAAT TCTTCGTAAT                
551                                                                       
    CTCCAACCAT GTCTGCCCTC TGCCACGGCC GCACCCTCTC GACATCCAAT                
601                                                                       
    CATCATCAAG GCAGGTGACT GGCAAGAATT CCGGGAAAAA CTGACGTTCT                
651                                                                       
    ATCTGGTTAC CCTTGAGCAA GCGCAGGAAC AACAGTAC (SEQ ID NO:84)              
Syntan3                                                                   
1  CATGGCTAAC TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA                 
51    GACCACCTGC ACCTTTGCTG GACCCGAACA ACCTCAATGA CGAAGACGTC              
101                                                                       
      TCTATCCTGA TGGACCGAAA CCTTCGACTT CCAAACCTGG AGAGCTTCGT              
151                                                                       
      AAGGGCTGTC AAGAACTTAG AAAATGCATC AGGTATTGAG GCAATTCTTC              
201                                                                       
      GTAATCTCCA ACCATGTCTG CCCTCTGCCA CGGCCGCACC CTCTCGACAT              
251                                                                       
      CCAATCATCA TCAAGGCAGG TGACTGGCAA GAATTCCGGG AAAAACTGAC              
301                                                                       
      GTTCTATCTG GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT              
351                                                                       
      CTGGCGGTGG CAGCGGCGGC GGTTCTAACT GCTCTATAAT GATCGATGAA              
401                                                                       
      ATTATACATC ACTTAAAGAG ACCACCTGCA CCTTTGCTGG ACCCGAACAA              
451                                                                       
      CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC CTTCGACTTC              
501                                                                       
      CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA              
551                                                                       
      GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC              
601                                                                       
      GGCCGCACCC TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG              
651                                                                       
      AATTCCGGGA AAAACTGACG TTCTATCTGG TTACCCTTGA GCAAGCGCAG              
701                                                                       
      GAACAACAGT AC (SEQ ID NO:85)                                        
pMON31104                                                                 
1  ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT                 
51    GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA              
101                                                                       
      AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG TAATCTCCAA              
151                                                                       
      CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC CAATCATCAT              
201                                                                       
      CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG TTCTATCTGG              
251                                                                       
      TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TAACTGCTCT              
301                                                                       
      ATAATGATCG ATGAAATTAT ACATCACTTA AAGAGACCAC CTGCACCTTT              
351                                                                       
      GTACGTAGAG GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT              
401                                                                       
      CTACTATCAA CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC              
451                                                                       
      ATGGCTACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG              
501                                                                       
      GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT              
551                                                                       
      CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC              
601                                                                       
      TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG              
651                                                                       
      CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC              
701                                                                       
      ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT              
751                                                                       
      CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG              
801                                                                       
      CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG              
851                                                                       
      AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC              
901                                                                       
      GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT              
951                                                                       
      GGCCCCTGCC CTGCAGCCCT AATAA (SEQ ID NO:86)                          
pMON31105                                                                 
1  ATGGCTAATG CATCAGGTAT TGAGGCAATT CTTCGTAATC TCCAACCATG                 
51    TCTGCCCTCT GCCACGGCCG CACCCTCTCG ACATCCAATC ATCATCAAGG              
101                                                                       
      CAGGTGACTG GCAAGAATTC CGGGAAAAAC TGACGTTCTA TCTGGTTACC              
151                                                                       
      CTTGAGCAAG CGCAGGAACA ACAGGGTGGT GGCTCTAACT GCTCTATAAT              
201                                                                       
      GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA CCTTTGCTGG              
251                                                                       
      ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC              
301                                                                       
      CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA              
351                                                                       
      ATACGTAGAG GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT              
401                                                                       
      CTACTATCAA CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC              
451                                                                       
      ATGGCTACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG              
501                                                                       
      GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT              
551                                                                       
      CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC              
601                                                                       
      TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG              
651                                                                       
      CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC              
701                                                                       
      ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT              
751                                                                       
      CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG              
801                                                                       
      CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG              
851                                                                       
      AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC              
901                                                                       
      GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT              
951                                                                       
      GGCCCCTGCC CTGCAGCCCT AATAA (SEQ ID NO:87)                          
pMON31106                                                                 
1  ATGGCTGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA                 
51    AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTT GAGCAAGCGC              
101                                                                       
      AGGAACAACA GGGTGGTGGC TCTAACTGCT CTATAATGAT CGATGAAATT              
151                                                                       
      ATACATCACT TAAAGAGACC ACCTGCACCT TTGCTGGACC CGAACAACCT              
201                                                                       
      CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT CGACTTCCAA              
251                                                                       
      ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT              
301                                                                       
      ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC              
351                                                                       
      CTACGTAGAG GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT              
401                                                                       
      CTACTATCAA CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC              
451                                                                       
      ATGGCTACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG              
501                                                                       
      GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT              
551                                                                       
      CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC              
601                                                                       
      TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG              
651                                                                       
      CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC              
701                                                                       
      ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT              
751                                                                       
      CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG              
801                                                                       
      CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG              
851                                                                       
      AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC              
901                                                                       
      GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT              
951                                                                       
      GGCCCCTGCC CTGCAGCCCT AATAA (SEQ ID NO:88)                          
pMON31107                                                                 
1  ATGGCTGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT                 
51    GGTTACCCTT GAGCAAGCGC AGGAACAACA GGGTGGTGGC TCTAACTGCT              
101                                                                       
      CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT              
151                                                                       
      TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA              
201                                                                       
      CCGAAACCTT CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA              
251                                                                       
      ACTTAGAAAA TGCATCAGGT ATTGAGGCAA TTCTTCGTAA TCTCCAACCA              
301                                                                       
      TGTCTGCCCT CTGCCACGGC CGCACCCTCT CGACATCCAA TCATCATCAA              
351                                                                       
      GTACGTAGAG GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT              
401                                                                       
      CTACTATCAA CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC              
451                                                                       
      ATGGCTACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG              
501                                                                       
      GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT              
551                                                                       
      CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC              
601                                                                       
      TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG              
651                                                                       
      CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC              
701                                                                       
      ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT              
751                                                                       
      CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG              
801                                                                       
      CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG              
851                                                                       
      AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC              
901                                                                       
      GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT              
951                                                                       
      GGCCCCTGCC CTGCAGCCCT AATAA (SEQ ID NO:89)                          
pMON31108                                                                 
1  ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT                 
51    GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA              
101                                                                       
      AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG TAATCTCCAA              
151                                                                       
      CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC CAATCATCAT              
201                                                                       
      CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG TTCTATCTGG              
251                                                                       
      TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TGGCGGTGGC              
301                                                                       
      AGCGGCGGCG GTTCTAACTG CTCTATAATG ATCGATGAAA TTATACATCA              
351                                                                       
      CTTAAAGAGA CCACCTGCAC CTTTGTACGT AGAGGGCGGT GGAGGCTCCC              
401                                                                       
      CGGGTGAACC GTCTGGTCCA ATCTCTACTA TCAACCCGTC TCCTCCGTCT              
451                                                                       
      AAAGAATCTC ATAAATCTCC AAACATGGCT ACCCAGGGTG CCATGCCGGC              
501                                                                       
      CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC              
551                                                                       
      ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG              
601                                                                       
      CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT              
651                                                                       
      AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC              
701                                                                       
      TGTGTGCCAC CTACAAGCTG TGCCACCCCG AGGAGCTGGT GCTGCTCGGA              
751                                                                       
      CACTCTCTGG GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC              
801                                                                       
      CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT              
851                                                                       
      ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC              
901                                                                       
      ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG              
951                                                                       
      GCAGCAGATG GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA               
            (SEQ ID NO:90)                                                
pMON31109                                                                 
1  ATGGCTAATG CATCAGGTAT TGAGGCAATT CTTCGTAATC TCCAACCATG                 
51   TCTGCCCTCT GCCACGGCCG CACCCTCTCG ACATCCAATC ATCATCAAGG               
101                                                                       
     CAGGTGACTG GCAAGAATTC CGGGAAAAAC TGACGTTCTA TCTGGTTACC               
151                                                                       
     CTTGAGCAAG CGCAGGAACA ACAGGGTGGT GGCTCTGGCG GTGGCAGCGG               
201                                                                       
     CGGCGGTTCT AACTGCTCTA TAATGATCGA TGAAATTATA CATCACTTAA               
251                                                                       
     AGAGACCACC TGCACCTTTG CTGGACCCGA ACAACCTCAA TGACGAAGAC               
301                                                                       
     GTCTCTATCC TGATGGACCG AAACCTTCGA CTTCCAAACC TGGAGAGCTT               
351                                                                       
     CGTAAGGGCT GTCAAGAACT TAGAATACGT AGAGGGCGGT GGAGGCTCCC               
401                                                                       
     CGGGTGAACC GTCTGGTCCA ATCTCTACTA TCAACCCGTC TCCTCCGTCT               
451                                                                       
     AAAGAATCTC ATAAATCTCC AAACATGGCT ACCCAGGGTG CCATGCCGGC               
501                                                                       
     CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC               
551                                                                       
     ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG               
601                                                                       
     CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT               
651                                                                       
     AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC               
701                                                                       
     TGTGTGCCAC CTACAAGCTG TGCCACCCCG AGGAGCTGGT GCTGCTCGGA               
751                                                                       
     CACTCTCTGG GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC               
801                                                                       
     CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT               
851                                                                       
     ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC               
901                                                                       
     ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG               
951                                                                       
     GCAGCAGATG GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA                
            (SEQ ID NO:91)                                                
pMON31110                                                                 
1  ATGGCTGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA                 
51   AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTT GAGCAAGCGC               
101                                                                       
     AGGAACAACA GGGTGGTGGC TCTGGCGGTG GCAGCGGCGG CGGTTCTAAC               
151                                                                       
     TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA GACCACCTGC               
201                                                                       
     ACCTTTGCTG GACCCGAACA ACCTCAATGA CGAAGACGTC TCTATCCTGA               
251                                                                       
     TGGACCGAAA CCTTCGACTT CCAAACCTGG AGAGCTTCGT AAGGGCTGTC               
301                                                                       
     AAGAACTTAG AAAATGCATC AGGTATTGAG GCAATTCTTC GTAATCTCCA               
351                                                                       
     ACCATGTCTG CCCTCTGCCA CGGCCTACGT AGAGGGCGGT GGAGGCTCCC               
401                                                                       
     CGGGTGAACC GTCTGGTCCA ATCTCTACTA TCAACCCGTC TCCTCCGTCT               
451                                                                       
     AAAGAATCTC ATAAATCTCC AAACATGGCT ACCCAGGGTG CCATGCCGGC               
501                                                                       
     CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC               
551                                                                       
     ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG               
601                                                                       
     CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT               
651                                                                       
     AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC               
701                                                                       
     TGTGTGCCAC CTACAAGCTG TGCCACCCCG AGGAGCTGGT GCTGCTCGGA               
751                                                                       
     CACTCTCTGG GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC               
801                                                                       
     CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT               
851                                                                       
     ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC               
901                                                                       
     ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG               
951                                                                       
     GCAGCAGATG GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA                
            (SEQ ID NO:92)                                                
pMON31111                                                                 
1  ATGGCTGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT                 
51    GGTTACCCTT GAGCAAGCGC AGGAACAACA GGGTGGTGGC TCTGGCGGTG              
101                                                                       
      GCAGCGGCGG CGGTTCTAAC TGCTCTATAA TGATCGATGA AATTATACAT              
151                                                                       
      CACTTAAAGA GACCACCTGC ACCTTTGCTG GACCCGAACA ACCTCAATGA              
201                                                                       
      CGAAGACGTC TCTATCCTGA TGGACCGAAA CCTTCGACTT CCAAACCTGG              
251                                                                       
      AGAGCTTCGT AAGGGCTGTC AAGAACTTAG AAAATGCATC AGGTATTGAG              
301                                                                       
      GCAATTCTTC GTAATCTCCA ACCATGTCTG CCCTCTGCCA CGGCCGCACC              
351                                                                       
      CTCTCGACAT CCAATCATCA TCAAGTACGT AGAGGGCGGT GGAGGCTCCC              
401                                                                       
      CGGGTGAACC GTCTGGTCCA ATCTCTACTA TCAACCCGTC TCCTCCGTCT              
451                                                                       
      AAAGAATCTC ATAAATCTCC AAACATGGCT ACCCAGGGTG CCATGCCGGC              
501                                                                       
      CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC              
551                                                                       
      ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG              
601                                                                       
      CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT              
651                                                                       
      AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC              
701                                                                       
      TGTGTGCCAC CTACAAGCTG TGCCACCCCG AGGAGCTGGT GCTGCTCGGA              
751                                                                       
      CACTCTCTGG GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC              
801                                                                       
      CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT              
851                                                                       
      ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC              
901                                                                       
      ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG              
951                                                                       
      GCAGCAGATG GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA               
             (SEQ ID NO:93)                                               
pMON13182                                                                 
1  ATGGCTAACTGCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                  
51     ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT             
101                                                                       
      CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA              
151                                                                       
      AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG              
201                                                                       
      TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC              
251                                                                       
      CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG              
301                                                                       
      TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG              
351                                                                       
      CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT              
401                                                                       
      ACAAGCTGTG CCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGGC              
451                                                                       
      ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC              
501                                                                       
      AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC              
551                                                                       
      TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA              
601                                                                       
      CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA              
651                                                                       
      AGAACTGGGA ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG              
701                                                                       
      CCTTCGCCTC TGCTTTCCAG CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC              
751                                                                       
      CATCTGCAGA GCTTCCTGGA GGTGTCGTAC CGCGTTCTAC GCCACCTTGC              
801                                                                       
      GCAGCCCTCT GGCGGCTCTG GCGGCTCTCA GAGCTTCCTG CTCAAGTCTT              
851                                                                       
      TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG              
901                                                                       
      CTGTGTGCCA CCTAATAA (SEQ ID NO:94)                                  
pMON13183                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51    ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT              
101                                                                       
      CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA              
151                                                                       
      AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG              
201                                                                       
      TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC              
251                                                                       
      CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG              
301                                                                       
      TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG              
351                                                                       
      CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC              
401                                                                       
      CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTACAAG              
451                                                                       
      CTGTGCCACC CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC              
501                                                                       
      CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT              
551                                                                       
     GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG               
601                                                                       
     GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA               
651                                                                       
     GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC               
701                                                                       
     TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GCCGGCCTTC               
751                                                                       
     GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT               
801                                                                       
     GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC               
851                                                                       
     CCTCTGGCGG CTCTGGCGGC TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG               
901                                                                       
     CAAGTGAGAA AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG               
951                                                                       
     TGCCACCTAA TAA (SEQ ID NO:95)                                        
pMON13184                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTC               
401                                                                       
     CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT               
451                                                                       
     GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT               
501                                                                       
     GCAGCCCACC CAGGGTGCCA TGCCGGCCTT CGCCTCTGCT TTCCAGCGCC               
551                                                                       
     GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT CCTGGAGGTG               
601                                                                       
     TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCTCTGGCG GCTCTGGCGG               
651                                                                       
     CTCTCAGAGC TTCCTGCTCA AGTCTTTAGA GCAAGTGAGA AAGATCCAGG               
701                                                                       
     GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CAAGCTGTGC               
751                                                                       
     CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC               
801                                                                       
     TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA               
851                                                                       
     GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG               
901                                                                       
     GAAGGGATAT CCTAATAA (SEQ ID NO:96)                                   
pMON13185                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC               
401                                                                       
     CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTCCCGAG               
451                                                                       
     TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC               
501                                                                       
     CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC               
551                                                                       
     CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA               
601                                                                       
     GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA               
651                                                                       
     CCGCGTTCTA CGCCACCTTG CGCAGCCCTC TGGCGGCTCT GGCGGCTCTC               
701                                                                       
     AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG TGAGAAAGAT CCAGGGCGAT               
751                                                                       
     GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC               
801                                                                       
     CGAGGAGCTG GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC               
851                                                                       
     TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA               
901                                                                       
     CTCCATAGCG GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG               
951                                                                       
     GATATCCTAA TAA (SEQ ID NO:97)                                        
pMON13186                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51     ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT             
101                                                                       
     CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA               
401                                                                       
     TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CTTCGCCTCT               
451                                                                       
     GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC ATCTGCAGAG               
501                                                                       
     CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG CAGCCCTCTG               
551                                                                       
     GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG               
601                                                                       
     AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC               
651                                                                       
     CTACAAGCTG TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG               
701                                                                       
     GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG               
751                                                                       
     GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT ACCAGGGGCT               
801                                                                       
     CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC ACCTTGGACA               
851                                                                       
     CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GCAGCAGATG               
901                                                                       
     GAAGAACTGG GATAATAA (SEQ ID NO:98)                                   
pMON13187                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC               
401                                                                       
     CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTATGGCC               
451                                                                       
     CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT               
501                                                                       
     CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC               
551                                                                       
     TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CTCTGGCGGC               
601                                                                       
     TCTGGCGGCT CTCAGAGCTT CCTGCTCAAG TCTTTAGAGC AAGTGAGAAA               
651                                                                       
     GATCCAGGGC GATGGCGCAG CGCTCCAGGA GAAGCTGTGT GCCACCTACA               
701                                                                       
     AGCTGTGCCA CCCCGAGGAG CTGGTGCTGC TCGGACACTC TCTGGGCATC               
751                                                                       
     CCCTGGGCTC CCCTGAGCTC CTGCCCCAGC CAGGCCCTGC AGCTGGCAGG               
801                                                                       
     CTGCTTGAGC CAACTCCATA GCGGCCTTTT CCTCTACCAG GGGCTCCTGC               
851                                                                       
     AGGCCCTGGA AGGGATATCC CCCGAGTTGG GTCCCACCTT GGACACACTG               
901                                                                       
     CAGCTGGACG TCGCCGACTT TGCCACCACC ATCTGGCAGC AGATGGAAGA               
951                                                                       
     ACTGGGATAA TAA (SEQ ID NO:99)                                        
pMON13188                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA               
401                                                                       
     CCCAGGGTGC CATGCCGGCC TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA               
451                                                                       
     GGGGTCCTGG TTGCTAGCCA TCTGCAGAGC TTCCTGGAGG TGTCGTACCG               
501                                                                       
     CGTTCTACGC CACCTTGCGC AGCCCTCTGG CGGCTCTGGC GGCTCTCAGA               
551                                                                       
     GCTTCCTGCT CAAGTCTTTA GAGCAAGTGA GAAAGATCCA GGGCGATGGC               
601                                                                       
     GCAGCGCTCC AGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA               
651                                                                       
     GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA               
701                                                                       
     GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC               
751                                                                       
    CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT                
801                                                                       
    ATCCCCCGAG TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG                
851                                                                       
    ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT                
901                                                                       
    GCCCTGCAGC CCTAATAA (SEQ ID NO:100)                                   
pMON13189                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51  ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT                
101                                                                       
    CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA                
151                                                                       
    AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG                
201                                                                       
    TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC                
251                                                                       
    CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG                
301                                                                       
    TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG                
351                                                                       
    CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC                
401                                                                       
    CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG                
451                                                                       
    GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT                
501                                                                       
    CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC                
551                                                                       
    TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC                
601                                                                       
    CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC                
651                                                                       
    GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC                
701                                                                       
    TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC                
751                                                                       
    TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG                
801                                                                       
    CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC                
851                                                                       
    CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT                
901                                                                       
    GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT                
951                                                                       
    GCAGCCCTAA TAA (SEQ ID NO:101)                                        
pMON13190                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51  ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT                
101                                                                       
    CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA                
151                                                                       
    AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG                
201                                                                       
    TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC                
251                                                                       
    CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG                
301                                                                       
    TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG                
351                                                                       
    CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT                
401                                                                       
    CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG                
451                                                                       
    AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTC                
501                                                                       
    TGGCGGCTCT GGCGGCTCTC AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG                
551                                                                       
    TGAGAAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC                
601                                                                       
    ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG GACACTCTCT                
651                                                                       
    GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC                
701                                                                       
    TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CTACCAGGGG                
751                                                                       
    CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC CCACCTTGGA                
801                                                                       
    CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATC TGGCAGCAGA                
851                                                                       
    TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCA GGGTGCCATG                
901                                                                       
    CCGGCCTTCG CCTAATAA (SEQ ID NO:102)                                   
pMON13191                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51  ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT                
101                                                                       
    CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA                
151                                                                       
    AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG                
201                                                                       
    TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC                
251                                                                       
    CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG                
301                                                                       
      TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG              
351                                                                       
      CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC              
401                                                                       
      CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTCTGCT              
451                                                                       
      TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT              
501                                                                       
      CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCTCTGGCG              
551                                                                       
      GCTCTGGCGG CTCTCAGAGC TTCCTGCTCA AGTCTTTAGA GCAAGTGAGA              
601                                                                       
      AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA              
651                                                                       
      CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA              
701                                                                       
      TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA              
751                                                                       
      GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT              
801                                                                       
      GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GGGTCCCACC TTGGACACAC              
851                                                                       
      TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCA GCAGATGGAA              
901                                                                       
      GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC              
951                                                                       
      CTTCGCCTAA TAA (SEQ ID NO:103)                                      
pMON13192                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51    ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT              
101                                                                       
      CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA              
151                                                                       
      AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG              
201                                                                       
      TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC              
251                                                                       
      CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG              
301                                                                       
      TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG              
351                                                                       
      CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT              
401                                                                       
      ACAAGCTGTG CCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGGC              
451                                                                       
      ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC              
501                                                                       
      AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC              
551                                                                       
      TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA              
601                                                                       
      CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA              
651                                                                       
      AGAACTGGGA ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG              
701                                                                       
      CCTTCGCCTC TGCTTTCCAG CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC              
751                                                                       
      CATCTGCAGA GCTTCCTGGA GGTGTCGTAC CGCGTTCTAC GCCACCTTGC              
801                                                                       
      GCAGCCCACA CCATTGGGCC CTGCCAGCTC CCTGCCCCAG AGCTTCCTGC              
851                                                                       
      TCAAGTCTTT AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC              
901                                                                       
      CAGGAGAAGC TGTGTGCCAC CTAATAA (SEQ ID NO:104)                       
pMON13193                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51    ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT              
101                                                                       
      CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA              
151                                                                       
      AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG              
201                                                                       
      TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC              
251                                                                       
      CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG              
301                                                                       
      TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG              
351                                                                       
      CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC              
401                                                                       
      CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTACAAG              
451                                                                       
      CTGTGCCACC CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC              
501                                                                       
      CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT              
551                                                                       
      GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG              
601                                                                       
      GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA              
651                                                                       
      GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC              
701                                                                       
      TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GCCGGCCTTC              
751                                                                       
      GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT              
801                                                                       
      GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC              
851                                                                       
      CCACACCATT GGGCCCTGCC AGCTCCCTGC CCCAGAGCTT CCTGCTCAAG              
901                                                                       
      TCTTTAGAGC AAGTGAGAAA GATCCAGGGC GATGGCGCAG CGCTCCAGGA              
951                                                                       
      GAAGCTGTGT GCCACCTAAT AA (SEQ ID NO:105)                            
pMON25190                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTC               
401                                                                       
     CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT               
451                                                                       
     GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT               
501                                                                       
     GCAGCCCACC CAGGGTGCCA TGCCGGCCTT CGCCTCTGCT TTCCAGCGCC               
551                                                                       
     GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT CCTGGAGGTG               
601                                                                       
     TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCACACCAT TGGGCCCTGC               
651                                                                       
     CAGCTCCCTG CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA               
701                                                                       
     AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC               
751                                                                       
     AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT               
801                                                                       
     CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG               
851                                                                       
     GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG               
901                                                                       
     CAGGCCCTGG AAGGGATATC CTAATAA (SEQ ID NO:106)                        
pMON25191                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC               
401                                                                       
     CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTCCCGAG               
451                                                                       
     TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC               
501                                                                       
     CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC               
551                                                                       
     CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA               
601                                                                       
     GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA               
651                                                                       
     CCGCGTTCTA CGCCACCTTG CGCAGCCCAC ACCATTGGGC CCTGCCAGCT               
701                                                                       
     CCCTGCCCCA GAGCTTCCTG CTCAAGTCTT TAGAGCAAGT GAGAAAGATC               
751                                                                       
     CAGGGCGATG GCGCAGCGCT CCAGGAGAAG CTGTGTGCCA CCTACAAGCT               
801                                                                       
     GTGCCACCCC GAGGAGCTGG TGCTGCTCGG ACACTCTCTG GGCATCCCCT               
851                                                                       
     GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG CCCTGCAGCT GGCAGGCTGC               
901                                                                       
     TTGAGCCAAC TCCATAGCGG CCTTTTCCTC TACCAGGGGCTCCTGCAGGC                
951                                                                       
     CCTGGAAGGG ATATCCTAAT AA (SEQ ID NO:107)                             
pMON13194                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA               
401                                                                       
     TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CTTCGCCTCT               
451                                                                       
     GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC ATCTGCAGAG               
501                                                                       
    CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG CAGCCCACAC                
551                                                                       
    CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTCTTTA                
601                                                                       
    GAGCAAGTGA GAAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT                
651                                                                       
    GTGTGCCACC TAqAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC                
701                                                                       
    ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC                
751                                                                       
    CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCC TTTTCCTCTA                
801                                                                       
    CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG TTGGGTCCCA                
851                                                                       
    CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG                
901                                                                       
    CAGCAGATGG AAGAACTGGG ATAATAA (SEQ ID NO:108)                         
pMON13195                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51  ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT                
101                                                                       
    CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA                
151                                                                       
    AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG                
201                                                                       
    TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC                
251                                                                       
    CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG                
301                                                                       
    TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG                
351                                                                       
    CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC                
401                                                                       
    CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTATGGCC                
451                                                                       
    CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT                
501                                                                       
    CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC                
551                                                                       
    TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CACACCATTG                
601                                                                       
    GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA                
651                                                                       
    AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG                
701                                                                       
    CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CGGACACTCT                
751                                                                       
    CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA                
801                                                                       
    GCTGGCAGGC TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG                
851                                                                       
    GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TCCCACCTTG                
901                                                                       
    GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA                
951                                                                       
    GATGGAAGAA CTGGGATAAT AA (SEQ ID NO:109)                              
pMON13196                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51  ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT                
101                                                                       
    CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA                
151                                                                       
    AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG                
201                                                                       
    TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC                
251                                                                       
    CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG                
301                                                                       
    TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG                
351                                                                       
    CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA                
401                                                                       
    CCCAGGGTGC CATGCCGGCC TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA                
451                                                                       
    GGGGTCCTGG TTGCTAGCCA TCTGCAGAGC TTCCTGGAGG TGTCGTACCG                
501                                                                       
    CGTTCTACGC CACCTTGCGC AGCCCACACC ATTGGGCCCT GCCAGCTCCC                
551                                                                       
    TGCCCCAGAG CTTCCTGCTC AAGTCTTTAG AGCAAGTGAG AAAGATCCAG                
601                                                                       
    GGCGATGGCG CAGCGCTCCA GGAGAAGCTG TGTGCCACCT ACAAGCTGTG                
651                                                                       
    CCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG                
701                                                                       
    CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG                
751                                                                       
    AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC TGCAGGCCCT                
801                                                                       
    GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA CTGCAGCTGG                
851                                                                       
    ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AGAACTGGGA                
901                                                                       
    ATGGCCCCTG CCCTGCAGCC CTAATAA (SEQ ID NO:110)                         
pMON13197                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51    ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT              
101                                                                       
      CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA              
151                                                                       
      AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG              
201                                                                       
      TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC              
251                                                                       
      CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG              
301                                                                       
      TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG              
351                                                                       
      CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC              
401                                                                       
      CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG              
451                                                                       
      GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT              
501                                                                       
      CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC              
551                                                                       
      TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC              
601                                                                       
      CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA              
651                                                                       
      TGGCGCAGCG CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC              
701                                                                       
      CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC CTGGGCTCCC              
751                                                                       
      CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA              
801                                                                       
      ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG              
851                                                                       
      GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC              
901                                                                       
      GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC              
951                                                                       
      CCCTGCCCTG CAGCCCTAAT AA (SEQ ID NO:111)                            
pMON13198                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51    ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT              
101                                                                       
      CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA              
151                                                                       
      AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG              
201                                                                       
      TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC              
251                                                                       
      CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG              
301                                                                       
      TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG              
351                                                                       
      CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT              
401                                                                       
      CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG              
451                                                                       
      AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCAC              
501                                                                       
      ACCATTGGGC CCTGCCAGCT CCCTGCCCCA GAGCTTCCTG CTCAAGTCTT              
551                                                                       
      TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG              
601                                                                       
      CTGTGTGCCA CCTACAAGCT GTGCCACCCC GAGGAGCTGG TGCTGCTCGG              
651                                                                       
      ACACTCTCTG GGCATCCCCT GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG              
701                                                                       
      CCCTGCAGCT GGCAGGCTGC TTGAGCCAAC TCCATAGCGG CCTTTTCCTC              
751                                                                       
      TACCAGGGGC TCCTGCAGGC CCTGGAAGGG ATATCCCCCG AGTTGGGTCC              
801                                                                       
      CACCTTGGAC ACACTGCAGC TGGACGTCGC CGACTTTGCC ACCACCATCT              
851                                                                       
      GGCAGCAGAT GGAAGAACTG GGAATGGCCC CTGCCCTGCA GCCCACCCAG              
901                                                                       
      GGTGCCATGC CGGCCTTCGC CTAATAA (SEQ ID NO:112)                       
pMON13199                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51    ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT              
101                                                                       
      CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA              
151                                                                       
      AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG              
201                                                                       
      TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC              
251                                                                       
      CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG              
301                                                                       
      TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG              
351                                                                       
      CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC              
401                                                                       
      CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTCTGCT              
451                                                                       
      TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT              
501                                                                       
      CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCACACCAT              
551                                                                       
      TGGGCCCTGC CAGCTCCCTG CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG              
601                                                                       
      CAAGTGAGAA AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG              
651                                                                       
      TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG CTCGGACACT              
701                                                                       
      CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG              
751                                                                       
     CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA               
801                                                                       
     GGGGCTCCTG CAGGCCCTGG AAGGGATATC CCCCGAGTTG GGTCCCACCT               
851                                                                       
     TGGACACACT GCAGCTGGAC GTCGCCGACT TTGCCACCAC CATCTGGCAG               
901                                                                       
     CAGATGGAAG AACTGGGAAT GGCCCCTGCC CTGCAGCCCA CCCAGGGTGC               
951                                                                       
     CATGCCGGCC TTCGCCTAAT AA (SEQ ID NO:113)                             
pMON31112                                                                 
1  ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA                 
51   GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG               
101                                                                       
     ATATCCTAAT GGACAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC               
151                                                                       
     CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA               
201                                                                       
     AAATCTCCTG CCATGTCTGC CGCTAGCCAC GGCCGCACCC ACGCGACATC               
251                                                                       
     CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC               
301                                                                       
     TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC               
401                                                                       
     CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG               
451                                                                       
     GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT               
501                                                                       
     CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC               
551                                                                       
     TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC               
601                                                                       
     CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC               
651                                                                       
     GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC               
701                                                                       
     TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC               
751                                                                       
     TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG               
801                                                                       
     CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC               
851                                                                       
     CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT               
901                                                                       
     GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT               
951                                                                       
     GCAGCCCTAA TAA (SEQ ID NO:114)                                       
pMON31113                                                                 
1  ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA                 
51   GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG               
101                                                                       
     ATATCCTGAT GGAAAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC               
151                                                                       
     CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA               
201                                                                       
     AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC ACGCGACATC               
251                                                                       
     CAATCATCAT CCGTGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC               
301                                                                       
     TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC               
401                                                                       
     CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG               
451                                                                       
     GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT               
501                                                                       
     CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC               
551                                                                       
     TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC               
601                                                                       
     CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA               
651                                                                       
     TGGCGCAGCG CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC               
701                                                                       
     CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC CTGGGCTCCC               
751                                                                       
     CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA               
801                                                                       
     ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG               
851                                                                       
     GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC               
901                                                                       
     GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC               
951                                                                       
     CCCTGCCCTG CAGCCCTAAT AA (SEQ ID NO:115)                             
pMON31114                                                                 
1  ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA                 
51   GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG               
101                                                                       
     ATATCCTGAT GGAAAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC               
151                                                                       
     CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA               
201                                                                       
    AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC ACGCGACATC                
251                                                                       
    CAATCATCAT CCGTGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC                
301                                                                       
    TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG                
351                                                                       
    CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC                
401                                                                       
    CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG                
451                                                                       
    GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT                
501                                                                       
    CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC                
551                                                                       
    TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC                
601                                                                       
    CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC                
651                                                                       
    GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC                
701                                                                       
    TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC                
751                                                                       
    TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG                
801                                                                       
    CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC                
851                                                                       
    CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT                
901                                                                       
    GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT                
951                                                                       
    GCAGCCCTAA TAA (SEQ ID NO:116)                                        
pMON31115                                                                 
1  ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA                 
51 GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG                 
101                                                                       
    ATATCCTAAT GGACAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC                
151                                                                       
    CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA                
201                                                                       
    AAATCTCCTG CCATGTCTGC CGCTAGCCAC GGCCGCACCC ACGCGACATC                
251                                                                       
    CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC                
301                                                                       
    TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG                
351                                                                       
    CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC                
401                                                                       
    CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG                
451                                                                       
    GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT                
501                                                                       
    CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC                
551                                                                       
    TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC                
601                                                                       
    CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA                
651                                                                       
    TGGCGCAGCG CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC                
701                                                                       
    CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC CTGGGCTCCC                
751                                                                       
    CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA                
801                                                                       
    ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG                
851                                                                       
    GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC                
901                                                                       
    GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC                
951                                                                       
    CCCTGCCCTG CAGCCCTAAT AA (SEQ ID NO:117)                              
pMON28505                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGAGGTTCACCCTTTGCCTACACCTGTCCTGC       
TGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACAT       
TCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGC       
CTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCC       
TTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAG       
CTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTC       
AGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAAC       
TGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCA (SEQ ID NO:118)           
pMON28506                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGTTGCCTACACCTGTCCTGCTGCCTGCTGTGG       
ACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGT       
GACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTC       
CTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGC       
TTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCT       
GCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGC       
GGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACT       
CCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCT (SEQ ID NO:119)           
pMON28507                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGTCCTGCTGCCTGCTGTGGACTTTAGCTTGG       
GAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCT       
GGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTT       
TCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGG       
GCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAA       
GGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCG       
TCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTC       
ACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCT (SEQ ID NO:120)           
pMON28508                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGTGGACTTTAGCTTGGGAGAATGGAAAA       
CCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGAT       
GGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTC       
CGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAG       
CTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCT       
GATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCG       
CCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGA       
GCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCT (SEQ ID NO:121)           
pMON28509                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGACTTTAGCTTGGGAGAATGGAAAACCCAGA       
TGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGC       
ACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTC       
CTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACA       
AGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCT       
TGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCT       
TGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGT       
GCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTG  (SEQ ID NO:122)          
pMON28510                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCGGTTACCCTTGAGCAAGCGCAGGAACAACAG       
TACGTAGAGGGCGGTGGAGGCTCCCCGGGGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCC       
TCCGTCTAAAGAATCTCATAAACTCCAAACATGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGG       
CACAGGACATTCTGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGA       
CCCACTTGCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCA       
GGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCATCTT       
CCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGGGGTCCACCCTCT       
GCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTGTGACCTCCGAGTCCTCAGT       
AAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGACCAGTGCCCAGAGGTTCACCCTTTGCC       
TACACCTGTCCTGCTGCCTGCTGTGGACTTTAGTTG  (SEQ ID NO:123)                     
pMON28511                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGACCCACTTGCCTCTCATCCCTCCTGGGGC       
AGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCC       
ACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGA       
GGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACA       
TGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGT       
CCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCT       
GTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAG       
CAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG  (SEQ ID NO:124)          
pMON28512                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAACCCAGCTTCCTCCACAGGGCAGGACCA       
CAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTT       
CCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCT       
CCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGAC       
TGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTT       
GGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTG       
CTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGC       
TTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT (SEQ ID NO:125)           
pMON28513                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGCAGGACCACAGCTCACAAGGATCCCAATG       
CCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTC       
CACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGA       
GTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTC       
ACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGAT       
GGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCA       
CGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCC       
TCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAG (SEQ ID NO:126)           
pMON28514                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCACAAGGATCCCAATGCCATCTTCCTGA       
GCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGT       
CAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAA       
CTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTA       
CACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAA       
GGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG       
GGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCC       
TGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACA (SEQ ID NO:127)           
pMON28515                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAAC       
ACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATT       
CGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGT       
GACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCC       
TGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGA       
CATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACT       
TGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCC       
TCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG (SEQ ID NO:128)           
pMON28516                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCATCTTCCTGAGCTTCCAACACCTGCTCC       
GAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAA       
CATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT       
GTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTG       
CTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGG       
AGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCA       
TCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAA       
CCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAAT (SEQ ID NO:129)           
pMON28519                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGAGGTTCACCCTTTGCCTACACCTGTCCTGC       
TGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACAT       
TCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGC       
CTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCC       
TTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAG       
CTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTC       
AGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGC       
TTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCA (SEQ ID NO:130)              
pMON28520                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGTTGCCTACACCTGTCCTGCTGCCTGCTGTGG       
ACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGT       
GACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTC       
CTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGC       
TTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCT       
GCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGC       
AACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCC       
ATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCT (SEQ ID NO:131)              
pMON28521                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGTCCTGCTGCCTGCTGTGGACTTTAGCTTGG       
GAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCT       
GGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTT       
TCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGG       
GCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAA       
GGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCT       
CCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACA       
GCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCT (SEQ ID NO:132)              
pMON28522                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGTGGACTTTAGCTTGGGAGAATGGAAAA       
CCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGAT       
GGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTC       
CGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAG       
CTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCT       
GATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCT       
GCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCC       
AGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCT (SEQ ID NO:133)              
pMON28523                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGACTTTAGCTTGGGAGAATGGAAAACCCAGA       
TGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGC       
ACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTC       
CTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACA       
AGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCT       
TGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGT       
GACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCC       
CAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTG  (SEQ ID NO:134)             
pMON28524                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAGAATGGAAAACCCAGATGGAGGAGACCA       
AGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACT       
GGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCC       
CTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATG       
CCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTC       
CACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTC       
CTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACC       
CTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTG (SEQ ID NO:135)              
pMON28525                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGACCCACTTGCCTCTCATCCCTCCTGGGGC       
AGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCC       
ACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGA       
GGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGG       
CGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCT       
TCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTG       
GACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAG       
TGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG (SEQ ID NO:136)              
pMON28526                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAACCCAGCTTCCTCCACAGGGCAGGACCA       
CAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTT       
CCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCG       
CCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGA       
GCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGG       
AGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTG       
GAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTT       
CTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT (SEQ ID NO:137)              
pMON28527                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGCAGGACCACAGCTCACAAGGATCCCAATG       
CCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTC       
CACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTC       
CTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACC       
CTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGA       
GGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGG       
GGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCC       
TTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAG (SEQ ID NO:138)              
pMON28528                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCACAAGGATCCCAATGCCATCTTCCTGA       
GCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGT       
CAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTG       
CTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACAC       
CTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGC       
ACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGA       
CCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGC       
AGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACA (SEQ ID NO:139)              
pMON28529                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAAC       
ACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATT       
CGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGAC       
TCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGC       
TGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACAT       
TCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGC       
CTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCC       
TTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG (SEQ ID NO:140)              
pMON28530                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCATCTTCCTGAGCTTCCAACACCTGCTCC       
GAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACAT       
GGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTC       
CTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTG       
TGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGC       
AGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCC       
CTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCC       
AGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAAT (SEQ ID NO:141)              
pMON28533                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTGACTTCCAAACCTG       
GAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATGAGGCAATTCTTCGTAATCT       
CCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGCATCCAATCATCATCAAGGCAGGTGACT       
GGCAAGAATTCCGGGAAAAACTGACGTTCTATTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTAC       
GTAGAGGGCGGTGGAGGCTCCCCGGTAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCG       
TCTAAAGAATCTCATAAATCTCCAAACATGGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTG       
CTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGG       
AGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCA       
TCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAA       
CCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCA       
ACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAA       
TTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTA       
AACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCA (SEQ ID NO:142)        
pMON28534                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGTTGCCTACACCTGTCCTGCTGCCTGCTGTGG       
ACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGT       
GACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTC       
CTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGC       
TTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCT       
GCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGC       
GGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGC       
TTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCT (SEQ ID          
NO:143)                                                                   
pMON28535                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGTCCTGCTGCCTGCTGTGGACTTTAGCTTGG       
GAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCT       
GGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTT       
TCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGG       
GCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAA       
GGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGC       
AACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCC       
ATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCT (SEQ ID          
NO:144)                                                                   
pMON28536                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTGTGGACTTTAGCTTGGGAGAATGGAAAA       
CCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGAT       
GGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTC       
CGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAG       
CTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCT       
GATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCC       
CCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACA       
GCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCT                  
(SEQ ID NO:145)                                                           
pMON28537                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGACTTTAGCTTGGGAGAATGGAAAACCCAGA       
TGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGC       
ACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTC       
CTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACA       
AGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCT       
TGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCG       
CCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGAC       
TGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTG                  
(SEQ ID NO:146)                                                           
pMON28538                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAGAATGGAAAACCCAGATGGAGGAGACCA       
AGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACT       
GGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCC       
CTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATG       
CCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTC       
CACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGT       
GACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCC       
CAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTG                  
(SEQ ID NO:147)                                                           
pMON28539                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGACCCACTTGCCTCTCATCCCTCCTGGGGC       
AGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCC       
ACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGA       
GGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACG       
GCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGA       
CTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTG       
CTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACA       
TTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG                  
(SEQ ID NO:148)                                                           
pMON28540                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGAACCCAGCTTCCTCCACAGGGCAGGACCA       
CAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTT       
CCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCG       
TCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTC       
ACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGA       
CTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTG       
ACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCC       
TGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT                  
(SEQ ID NO:149)                                                           
pMON28541                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGGCAGGACCACAGCTCACAAGGATCCCAATG       
CCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTC       
CACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGT       
GACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGqAGACTGAGCCAGTGCC       
CAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAA       
AACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTG       
ATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGG       
TCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAG                  
(SEQ ID NO:150)                                                           
pMON28542                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCTCACAAGGATCCCAATGCCATCTTCCTGA       
GCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGT       
CAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTC       
CTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACC       
CTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGA       
GGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGG       
GGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCC       
TTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACA                  
(SEQ ID NO:151)                                                           
pMON28543                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAAC       
ACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATT       
CGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAA       
CTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTA       
CACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAA       
GGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG       
GGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCC       
TGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG                  
(SEQ ID NO:152)                                                           
pMON28544                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGCCATCTTCCTGAGCTTCCAACACCTGCTCC       
GAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAA       
CGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGT       
GACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCC       
TGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGA       
CATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACT       
TGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCC       
TCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAAT                  
(SEQ ID NO:153)                                                           
pMON28545                                                                 
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTTGCTGG       
ACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGACTTCCAAACCT       
GGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAGGCAATTCTTCGTAAT       
CTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCCAATCATCATCAAGGCAGGTG       
ACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTACCCTTGAGCAAGCGCAGGAACAACA       
GTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCT       
CCTCCGTCTAAAGAATCTCATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAAC       
ACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATT       
CGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGT       
GACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCC       
TGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGA       
CATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACT       
TGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCC       
TCCTTGGAACCCAGGGCAGGACCACAGCTCACAAG  (SEQ ID NO:154)                      
pMON15981                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51  ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT                
101                                                                       
    CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA                
151                                                                       
    AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG                
201                                                                       
    TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC                
251                                                                       
    CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG                
301                                                                       
    TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG                
351                                                                       
    CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC                
401                                                                       
    CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTTACAAG                
451                                                                       
   CTGTGCCACC CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC                 
501                                                                       
   CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT                 
551                                                                       
   GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG                 
601                                                                       
   GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA                 
651                                                                       
   GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC                 
701                                                                       
   TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GCCGGCCTTC                 
751                                                                       
   GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT                 
801                                                                       
   GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC                 
851                                                                       
   CCGGCGGCGG CTCTGACATG GCTACACCAT TAGGCCCTGC CAGCTCCCTG                 
901                                                                       
   CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGGA AGATCCAGGG                 
951                                                                       
   CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAA TAA;                       
         (SEQ ID NO:155)                                                  
pMON15982                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT                 
101                                                                       
   CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA                 
151                                                                       
   AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG                 
201                                                                       
   TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC                 
251                                                                       
   CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG                 
301                                                                       
   TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG                 
351                                                                       
   CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC                 
401                                                                       
   CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTCCCGAG                 
451                                                                       
   TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC                 
501                                                                       
   CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC                 
551                                                                       
   CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA                 
601                                                                       
   GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA                 
651                                                                       
   CCGCGTTCTA CGCCACCTTG CGCAGCCCqG CGGCGGCTCT GACATGGCTA                 
701                                                                       
   CACCATTAGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT                 
751                                                                       
   TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA                 
801                                                                       
   GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG                 
851                                                                       
   GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG                 
901                                                                       
   GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT                 
951                                                                       
   CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCTAA TAA;                       
         (SEQ ID NO:156)                                                  
pMON15965                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT                 
101                                                                       
   CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA                 
151                                                                       
   AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG                 
201                                                                       
   TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC                 
251                                                                       
   CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG                 
301                                                                       
   TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG                 
351                                                                       
   CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC                 
401                                                                       
   CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTTCTGCT                 
451                                                                       
   TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT                 
501                                                                       
   CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCGGCGGCG                 
551                                                                       
   GCTCTGACAT GGCTACACCA TTAGGCCCTG CCAGCTCCCT GCCCCAGAGC                 
601                                                                       
   TTCCTGCTCA AGTCTTTAGA GCAAGTGAGG AAGATCCAGG GCGATGGCGC                 
651                                                                       
   AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG                 
701                                                                       
   AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC                 
751                                                                       
   TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA GCCAACTCCA                 
801                                                                       
   TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG GAAGGGATAT                 
851                                                                       
   CCCCCGAGTT GGGTCCCACC TTGGACACAC TGCAGCTGGA CGTCGCCGAC                 
901                                                                       
   TTTGCCACCA CCATCTGGCA GCAGATGGAA GAACTGGGAA TGGCCCCTGC                 
951                                                                       
   CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CTTCGCCTAA TAA                        
         (SEQ ID NO:157)                                                  
pMON15966                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC               
401                                                                       
     CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTATGGCC               
451                                                                       
     CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT               
501                                                                       
     CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC               
551                                                                       
     TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CGGCGGCGGC               
601                                                                       
     TCTGACATGG CTACACCATT AGGCCCTGCC AGCTCCCTGC CCCAGAGCTT               
651                                                                       
     CCTGCTCAAG TCTTTAGAGC AAGTGAGGAA GATCCAGGGC GATGGCGCAG               
701                                                                       
     CGCTCCAGGA GAAGCTGTGT GCCACCTACA AGCTGTGCCA CCCCGAGGAG               
751                                                                       
     CTGGTGCTGC TCGGACACTC TCTGGGCATC CCCTGGGCTC CCCTGAGCTC               
801                                                                       
     CTGCCCCAGC CAGGCCCTGC AGCTGGCAGG CTGCTTGAGC CAACTCCATA               
851                                                                       
     GCGGCCTTTT CCTCTACCAG GGGCTCCTGC AGGCCCTGGA AGGGATATCC               
901                                                                       
     CCCGAGTTGG GTCCCACCTT GGACACACTG CAGCTGGACG TCGCCGACTT               
951                                                                       
     TGCCACCACC ATCTGGCAGC AGATGGAAGA ACTGGGATAA TAA                      
            (SEQ ID NO:158)                                               
pMON15967                                                                 
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC               
401                                                                       
     CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTACCCAG               
451                                                                       
     GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT               
501                                                                       
     CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC               
551                                                                       
     TACGCCACCT TGCGCAGCCC GGCGGCGGCT CTGACATGGC TACACCATTA               
601                                                                       
     GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA               
651                                                                       
     AGTGAGGAAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG               
701                                                                       
     CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CGGACACTCT               
751                                                                       
     CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA               
801                                                                       
     GCTGGCAGGC TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG               
851                                                                       
     GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TCCCACCTTG               
901                                                                       
     GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA               
951                                                                       
     GATGGAAGAA CTGGGAATGG CCCCTGCCCT GCAGCCCTAA TAA                      
            (SEQ ID NO:159)                                               
pMON15960                                                                 
1  ATGGCTACAC CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT                 
51   CAAGTCTTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC               
101                                                                       
     AGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTG               
151                                                                       
     CTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCC               
201                                                                       
     CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCC               
251                                                                       
     TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG               
301                                                                       
     TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC               
351                                                                       
     CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC               
401                                                                       
     CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA               
451                                                                       
     GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA               
501                                                                       
     CCGCGTTCTA CGCCACCTTG CGCAGCCCGG CGGCGGCTCT GACATGGCTA               
551                                                                       
     CACCATTGGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT               
601                                                                       
     TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA               
651                                                                       
     GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG               
701                                                                       
     GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG               
751                                                                       
     GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT               
801                                                                       
     CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC               
851                                                                       
     CCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATC               
901                                                                       
     TGGCAGCAGA TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCA               
1001                                                                      
     TCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTT               
1051                                                                      
     CTACGCCACC TTGCGCAGCC CTGATAA (SEQ ID NO:160)                        
PM0N32132                                                                 
TCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTC       
ACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGA       
CTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTG       
ACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCC       
TGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCT       
TCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTG       
CTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG                 
(SEQ ID NO:249)                                                           
PMON32133                                                                 
TCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTC       
ACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGA       
CTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTG       
ACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCC       
TGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGGG       
CAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAG       
GTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG (SEQ ID NO:250)             
pMON32134                                                                 
TCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTC       
ACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGA       
CTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTG       
ACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCC       
TGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCT       
TCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTG       
CTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG                 
(SEQ ID NO:251)                                                           
Pmon13181                                                                 
1  CCATGGCTAA CTGCTCTATA ATGATCGATG AAATTATACA TCACTTAAAG                 
51   AGACCACCTG CACCTTTGCT GGACCCGAAC AACCTCAATG ACGAAGACGT               
101                                                                       
     CTCTATCCTG ATGGATCGAA ACCTTCGACT TCCAAACCTG GAGAGCTTCG               
151                                                                       
     TAAGGGCTGT CAAGAACTTA GAAAATGCAT CAGGTATTGA GGCAATTCTT               
201                                                                       
     CGTAATCTCC AACCATGTCT GCCCTCTGCC ACGGCCGCAC CCTCTCGACA               
251                                                                       
     TCCAATCATC ATCAAGGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA               
301                                                                       
     CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GTACGTAgag               
351                                                                       
     ggcggtggag gctcCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA               
401                                                                       
     CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC ATGTAAGGTA               
451                                                                       
     CCGCATGCAA GCTT (SEQ ID NO:257)                                      
Pmon13180.Seg                                                             
1  CCATGGCTAA CTGCTCTATA ATGATCGATG AAATTATACA TCACTTAAAG                 
51   AGACCACCTG CACCTTTGCT GGACCCGAAC AACCTCAATG ACGAAGACGT               
101                                                                       
     CTCTATCCTG ATGGATCGAA ACCTTCGACT TCCAAACCTG GAGAGCTTCG               
151                                                                       
     TAAGGGCTGT CAAGAACTTA GAAAATGCAT CAGGTATTGA GGCAATTCTT               
201                                                                       
     CGTAATCTCC AACCATGTCT GCCCTCTGCC ACGGCCGCAC CCTCTCGACA               
251                                                                       
     TCCAATCATC ATCAAGGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA               
301                                                                       
     CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GTACGTAgag               
351                                                                       
     ggcggtggag gctcCCCGGG TGGTGGTTCT GGCGGCGGCT CCAACATGTA               
401                                                                       
     AGGTACCGCA TGCAAGCTT (SEQ ID NO:258)                                 
pmon16017.seq                                                             
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC               
401                                                                       
     CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTTAGGC               
451                                                                       
     CCTGCCAGCT CCCTGCCCCA GAGCTTCCTG CTCAAGTCTT TAGAGCAAGT               
501                                                                       
     GAGGAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG CTGTGTGCCA               
551                                                                       
     CCTACAAGCT GTGCCACCCC GAGGAGCTGG TGCTGCTCGG ACACTCTCTG               
601                                                                       
     GGCATCCCCT GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG CCCTGCAGCT               
651                                                                       
     GGCAGGCTGC TTGAGCCAAC TCCATAGCGG CCTTTTCCTC TACCAGGGGC               
701                                                                       
     TCCTGCAGGC CCTGGAAGGG ATATCCCCCG AGTTGGGTCC CACCTTGGAC               
751                                                                       
     ACACTGCAGC TGGACGTCGC CGACTTTGCC ACCACCATCT GGCAGCAGAT               
801                                                                       
     GGAAGAACTG GGAATGGCCC CTGCCCTGCA GCCCACCCAG GGTGCCATGC               
851                                                                       
     CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT               
901                                                                       
     AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC TACGCCACCT               
951                                                                       
     TGCGCAGCCC GACATGGCTA CACCA (SEQ ID NO:259)                          
pmon16018.seq                                                             
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC               
401                                                                       
     CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTCAGAGC               
451                                                                       
     TTCCTGCTCA AGTCTTTAGA GCAAGTGAGG AAGATCCAGG GCGATGGCGC               
501                                                                       
     AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG               
551                                                                       
     AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC               
601                                                                       
     TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA GCCAACTCCA               
651                                                                       
     TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG GAAGGGATAT               
701                                                                       
     CCCCCGAGTT GGGTCCCACC TTGGACACAC TGCAGCTGGA CGTCGCCGAC               
751                                                                       
     TTTGCCACCA CCATCTGGCA GCAGATGGAA GAACTGGGAA TGGCCCCTGC               
801                                                                       
     CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC               
851                                                                       
     GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG               
901                                                                       
     GTGTCGTACC GCGTTCTACG CCACCTTGCG CAGCCCGACA TGGCTACACC               
951                                                                       
     ATTAGGCCCT GCCAGCTCCC TGCCC (SEQ ID NO:260)                          
pmon16019.seq                                                             
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT                 
101                                                                       
   CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA                 
151                                                                       
   AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG                 
201                                                                       
   TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC                 
251                                                                       
   CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG                 
301                                                                       
   TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG                 
351                                                                       
   CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC                 
401                                                                       
   CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTTCCTG                 
451                                                                       
   CTCAAGTCTT TAGAGCAAGT GAGGAAGATC CAGGGCGATG GCGCAGCGCT                 
501                                                                       
   CCAGGAGAAG CTGTGTGCCA CCTACAAGCT GTGCCACCCC GAGGAGCTGG                 
551                                                                       
   TGCTGCTCGG ACACTCTCTG GGCATCCCCT GGGCTCCCCT GAGCTCCTGC                 
601                                                                       
   CCCAGCCAGG CCCTGCAGCT GGCAGGCTGC TTGAGCCAAC TCCATAGCGG                 
651                                                                       
   CCTTTTCCTC TACCAGGGGC TCCTGCAGGC CCTGGAAGGG ATATCCCCCG                 
701                                                                       
   AGTTGGGTCC CACCTTGGAC ACACTGCAGC TGGACGTCGC CGACTTTGCC                 
751                                                                       
   ACCACCATCT GGCAGCAGAT GGAAGAACTG GGAATGGCCC CTGCCCTGCA                 
801                                                                       
   GCCCACCCAG GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG                 
851                                                                       
   CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG                 
901                                                                       
   TACCGCGTTC TACGCCACCT TGCGCAGCCC GACATGGCTA CACCATTAGG                 
951                                                                       
   CCCTGCCAGC TCCCTGCCCC AGAGC (SEQ ID NO:261)                            
pmon16020.seq                                                             
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT                 
101                                                                       
   CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA                 
151                                                                       
   AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG                 
201                                                                       
   TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC                 
251                                                                       
   CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG                 
301                                                                       
   TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG                 
351                                                                       
   CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC                 
401                                                                       
   CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTGAGCAA                 
451                                                                       
   GTGAGGAAGA TCCAGGGCGA TGGCGCAGCG CTCCAGGAGA AGCTGTGTGC                 
501                                                                       
   CACCTACAAG CTGTGCCACC CCGAGGAGCT GGTGCTGCTC GGACACTCTC                 
551                                                                       
   TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG                 
601                                                                       
   CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG                 
651                                                                       
   GCTCCTGCAG GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG                 
701                                                                       
   ACACACTGCA GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG                 
751                                                                       
   ATGGAAGAAC TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT                 
801                                                                       
   GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG                 
851                                                                       
   CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC                 
901                                                                       
   CTTGCGCAGC CCGACATGGC TACACCATTA GGCCCTGCCA GCTCCCTGCC                 
951                                                                       
   CCAGAGCTTC CTGCTCAAGT CTTTA (SEQ ID NO:262)                            
pmon16021.seq                                                             
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT                 
101                                                                       
   CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA                 
151                                                                       
   AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG                 
201                                                                       
   TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC                 
251                                                                       
   CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG                 
301                                                                       
   TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG                 
351                                                                       
   CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC                 
401                                                                       
   CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTCTGCTC                 
451                                                                       
   GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA                 
501                                                                       
   GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC                 
551                                                                       
   TCTACCAGGG GCTCCTGCAG GCCCTGGAAG GGATATCCCC CGAGTTGGGT                 
601                                                                       
   CCCACCTTGG ACACACTGCA GCTGGACGTC GCCGACTTTG CCACCACCAT                 
651                                                                       
   CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CCCTGCCCTG CAGCCCACCC                 
701                                                                       
     AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG               
751                                                                       
     GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT               
801                                                                       
     TCTACGCCAC CTTGCGCAGC CCGACATGGC TACACCATTA GGCCCTGCCA               
851                                                                       
     GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA AGTGAGGAAG               
901                                                                       
     ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG CCACCTACAA               
951                                                                       
     GCTGTGCCAC CCCGAGGAGC TGGTG (SEQ ID NO:263)                          
pmon16022.seq                                                             
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC               
401                                                                       
     CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTCCCCTG               
451                                                                       
     AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT               
501                                                                       
     CCATAGCGGC CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA               
551                                                                       
     TATCCCCCGA GTTGGGTCCC ACCTTGGACA CACTGCAGCT GGACGTCGCC               
601                                                                       
     GACTTTGCCA CCACCATCTG GCAGCAGATG GAAGAACTGG GAATGGCCCC               
651                                                                       
     TGCCCTGCAG CCCACCCAGG GTGCCATGCC GGCCTTCGCC TCTGCTTTCC               
701                                                                       
     AGCGCCGGGC AGGAGGGGTC CTGGTTGCTA GCCATCTGCA GAGCTTCCTG               
751                                                                       
     GAGGTGTCGT ACCGCGTTCT ACGCCACCTT GCGCAGCCCG ACATGGCTAC               
801                                                                       
     ACCATTAGGC CCTGCCAGCT CCCTGCCCCA GAGCTTCCTG CTCAAGTCTT               
851                                                                       
     TAGAGCAAGT GAGGAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG               
901                                                                       
     CTGTGTGCCA CCTACAAGCT GTGCCACCCC GAGGAGCTGG TGCTGCTCGG               
951                                                                       
     ACACTCTCTG GGCATCCCCT GGGCT (SEQ ID NO:264)                          
pmon16023.seq                                                             
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC               
401                                                                       
     CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTCAGGCC               
451                                                                       
     CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCC TTTTCCTCTA               
501                                                                       
     CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG TTGGGTCCCA               
551                                                                       
     CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG               
601                                                                       
     CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG               
651                                                                       
     TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC               
701                                                                       
     TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA               
751                                                                       
     CGCCACCTTG CGCAGCCCGA CATGGCTACA CCATTAGGCC CTGCCAGCTC               
801                                                                       
     CCTGCCCCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG AGGAAGATCC               
851                                                                       
     AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CTACAAGCTG               
901                                                                       
     TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG               
951                                                                       
     GGCTCCCCTG AGCTCCTGCC CCAGC (SEQ ID NO:265)                          
pmon16024.seq                                                             
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
      AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG              
201                                                                       
      TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC              
251                                                                       
      CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG              
301                                                                       
      TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG              
351                                                                       
      CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC              
401                                                                       
      CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTCTGCAG              
451                                                                       
      CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG              
501                                                                       
      GCTCCTGCAG GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG              
551                                                                       
     ACACACTGCA GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG               
601                                                                       
     ATGGAAGAAC TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT               
651                                                                       
     GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG               
701                                                                       
     CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC               
751                                                                       
     CTTGCGCAGC CCGACATGGC TACACCATTA GGCCCTGCCA GCTCCCTGCC               
801                                                                       
     CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA AGTGAGGAAG ATCCAGGGCG               
851                                                                       
     ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC               
901                                                                       
     CCCGAGGAGC TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC               
951                                                                       
     CCTGAGCTCC TGCCCCAGCC AGGCC (SEQ ID NO:266)                          
pmon16025.seq                                                             
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC               
401                                                                       
     CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTCTGGCA               
451                                                                       
     GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT               
501                                                                       
     GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GGGTCCCACC TTGGACACAC               
551                                                                       
     TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCA GCAGATGGAA               
601                                                                       
     GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC               
651                                                                       
     CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC               
701                                                                       
     ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG               
751                                                                       
     CAGCCCGACA TGGCTACACC ATTAGGCCCT GCCAGCTCCC TGCCCCAGAG               
801                                                                       
     CTTCCTGCTC AAGTCTTTAG AGCAAGTGAG GAAGATCCAG GGCGATGGCG               
851                                                                       
     CAGCGCTCCA GGAGAAGCTG TGTGCCACCT ACAAGCTGTG CCACCCCGAG               
901                                                                       
     GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG CTCCCCTGAG               
951                                                                       
     CTCCTGCCCC AGCCAGGCCC TGCAG (SEQ ID NO:267)                          
pmon16026.seq                                                             
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC               
401                                                                       
     CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTGAACTG               
451                                                                       
     GGAATGGCCC CTGCCCTGCA GCCCACCCAG GGTGCCATGC CGGCCTTCGC               
501                                                                       
     CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC               
551                                                                       
     AGAGCTTCCT GGAGGTGTCG TACCGCGTTC TACGCCACCT TGCGCAGCCC               
601                                                                       
     GACATGGCTA CACCATTAGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT               
651                                                                       
     GCTCAAGTCT TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC               
701                                                                       
     TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG               
751                                                                       
     GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG               
801                                                                       
     CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG               
851                                                                       
     GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCCCC               
901                                                                       
     GAGTTGGGTC CCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC               
951                                                                       
     CACCACCATC TGGCAGCAGA TGGAA (SEQ ID NO:268)                          
pmon16027.seq                                                             
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC               
401                                                                       
     CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTGGAATG               
451                                                                       
     GCCCCTGCCC TGCAGCCCAC CCAGGGTGCC ATGCCGGCCT TCGCCTCTGC               
501                                                                       
     TTTCCAGCGC CGGGCAGGAG GGGTCCTGGT TGCTAGCCAT CTGCAGAGCT               
551                                                                       
     TCCTGGAGGT GTCGTACCGC GTTCTACGCC ACCTTGCGCA GCCCGACATG               
601                                                                       
     GCTACACCAT TAGGCCCTGC CAGCTCCCTG CCCCAGAGCT TCCTGCTCAA               
651                                                                       
     GTCTTTAGAG CAAGTGAGGA AGATCCAGGG CGATGGCGCA GCGCTCCAGG               
701                                                                       
     AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG               
751                                                                       
     CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG               
801                                                                       
     CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT               
851                                                                       
     TCCTCTACCA GGGGCTCCTG CAGGCCCTGG AAGGGATATC CCCCGAGTTG               
901                                                                       
     GGTCCCACCT TGGACACACT GCAGCTGGAC GTCGCCGACT TTGCCACCAC               
951                                                                       
     CATCTGGCAG CAGATGGAAG AACTG (SEQ ID NO:269)                          
pmon16028.seq                                                             
1  ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG                 
51   ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT               
101                                                                       
     CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA               
151                                                                       
     AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG               
201                                                                       
     TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC               
251                                                                       
     CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG               
301                                                                       
     TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG               
351                                                                       
     CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC               
401                                                                       
     CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTAGCTTC               
451                                                                       
     CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCGACATGGC               
501                                                                       
     TACACCATTA GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT               
551                                                                       
     CTTTAGAGCA AGTGAGGAAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG               
601                                                                       
     AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT               
651                                                                       
     CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC               
701                                                                       
     AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG CGGCCTTTTC               
751                                                                       
     CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG               
801                                                                       
     TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA               
851                                                                       
     TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT GCAGCCCACC               
901                                                                       
     CAGGGTGCCA TGCCGGCCTT CGCCTCTGCT TTCCAGCGCC GGGCAGGAGG               
951                                                                       
     GGTCCTGGTT GCTAGCCATC TGCAG (SEQ ID NO:270)                          
1     ATGGCTGGAC CCACTTGCCT CTCATCCCTC CTGGGGCAGC TTTCTGGACA              
51   GGTCCGTCTC CTCCTTGGGG CCCTGCAGAG CCTCCTTGGA ACCCAGCTTC               
101                                                                       
     CTCCACAGGG CAGGACCACA GCTCACAAGG ATCCCAATGC CATCTTCCTG               
151                                                                       
     AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG CGTTTCCTGA TGCTTGTAGG               
201                                                                       
     AGGGTCCACC CTCGCCGTCA GGGAATTCGG CGGCAACATG GCGTCTCCGG               
251                                                                       
     CGCCGCCTGC TGCTGACCTC CGAGTCCTCA GTAAACTGCT TCGTGACTCC               
301                                                                       
     CATGTCCTTC ACAGCAGACT GAGCCAGTGC CCAGAGGTTC ACCCTTTGCC               
351                                                                       
     TACACCTGTC CTGCTGCCTG CTGTGGACTT TAGCTTGGGA GAATGGAAAA               
401                                                                       
     CCCAGATGGA GGAGACCAAG GCACAGGACA TTCTGGGAGC AGTGACCCTT               
451                                                                       
    CTGCTGGAGG GAGTGATGGC AGCACGGGGA CAACTG                               
           (SEQ ID NO:286)                                                
1   ATGGCTGGCA GGACCACAGC TCACAAGGAT CCCAATGCCA TCTTCCTGAG                
51  CTTCCAACAC CTGCTCCGAG GAAAGGTGCG TTTCCTGATG CTTGTAGGAG                
101                                                                       
    GGTCCACCCT CGCCGTCAGG GAATTCGGCG GCAACATGGC GTCTCCGGCG                
151                                                                       
    CCGCCTGCTG CTGACCTCCG AGTCCTCAGT AAACTGCTTC GTGACTCCCA                
201                                                                       
    TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AGAGGTTCAC CCTTTGCCTA                
251                                                                       
    CACCTGTCCT GCTGCCTGCT GTGGACTTTA GCTTGGGAGA ATGGAAAACC                
301                                                                       
    CAGATGGAGG AGACCAAGGC ACAGGACATT CTGGGAGCAG TGACCCTTCT                
351                                                                       
    GCTGGAGGGA GTGATGGCAG CACGGGGACA ACTGGGACCC ACTTGCCTCT                
401                                                                       
    CATCCCTCCT GGGGCAGCTT TCTGGACAGG TCCGTCTCCT CCTTGGGGCC                
451                                                                       
    CTGCAGAGCC TCCTTGGAAC CCAGCTTCCT CCACAG                               
           (SEQ ID NO:287)                                                
__________________________________________________________________________

                                  TABLE 3                                 
__________________________________________________________________________
PROTEIN SEQUENCES                                                         
__________________________________________________________________________
pMON26458pep                                                              
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis              
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu              
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla              
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln              
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu              
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla              
HisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg              
PheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe                             
(SEQ ID NO:161)                                                           
pMON28548pep                                                              
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis              
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu              
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla              
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln              
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu              
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla              
HisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg              
PheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAla              
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis              
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu              
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla              
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln              
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu              
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnGlyArgThrThrAlaHisLysAspPro              
AsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeu              
ValGlyGlySerThrLeuCysValArg (SEQ ID NO:162)                               
pMON28500                                                                 
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeu        
HisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaVal        
AspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAla        
ValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSer        
LeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThr        
GlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGln        
HisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGlu        
PheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArg        
AspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVal        
LeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGln        
AspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyPro        
ThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGln        
SerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIle        
PheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThr        
LeuCysValArg (SEQ ID NO:163)                                              
pMON28501                                                                 
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis              
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu              
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla              
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln              
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu              
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla              
HisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg              
PheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAla              
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis              
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu              
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla              
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln              
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu              
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla              
HisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg              
PheLeuMetLeuValGlyGlySerThrLeuCysValArg (SEQ ID NO:164)                   
pMON28502                                                                 
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis              
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu              
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla              
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln              
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu              
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla              
HisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg              
PheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGly              
AsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArg              
AspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThr              
ProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu              
ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAla              
ArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnVal              
ArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArg              
ThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGly              
LysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg                          
(SEQ ID NO:165)                                                           
13182.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Tyr Lys Leu Cys               
His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro               
Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala               
Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly               
Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr               
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile               
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly               
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val               
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys               
Ala Thr (SEQ ID NO:166)                                                   
13183.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Tyr Lys Leu Cys               
His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro               
Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala               
Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly               
Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr               
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile               
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly               
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val               
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys               
Ala Thr (SEQ ID NO:167)                                                   
13184.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Pro Glu Leu Gly               
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr               
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu               
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser               
Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu               
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys               
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu               
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys               
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His               
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly               
Ile Ser (SEQ ID NO:168)                                                   
13185.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Pro Glu Leu Gly               
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr               
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu               
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser               
Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu               
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys               
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu               
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys               
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His               
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly               
Ile Ser (SEQ ID NO:169)                                                   
13186.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Met Ala Pro Ala               
Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe               
Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser               
Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro               
Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu               
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu               
Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val               
Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser               
Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu               
His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu               
Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu               
Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu               
Leu Gly (SEQ ID NO:170)                                                   
13187.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Met Ala Pro Ala               
Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe               
Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser               
Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro               
Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu               
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu               
Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val               
Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser               
Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu               
His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu               
Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu               
Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu               
Leu Gly (SEQ ID NO:171)                                                   
13188.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Thr Gln Gly Ala               
Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val               
Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg               
Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser               
Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln               
Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys               
Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly               
Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln               
Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr               
Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly               
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr               
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu               
Gln Pro (SEQ ID NO:172)                                                   
13189.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala               
Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val               
Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg               
Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser               
Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln               
Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys               
Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly               
Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln               
Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr               
Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly               
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr               
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu               
Gln Pro (SEQ ID NO:173)                                                   
13190.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser               
Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu               
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys               
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu               
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys               
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His               
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly               
Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp               
Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu               
Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala               
Phe Ala (SEQ ID NO:174)                                                   
13191.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser               
Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu               
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys               
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu               
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys               
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His               
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly               
Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp               
Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu               
Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala               
Phe Ala (SEQ ID NO:175)                                                   
13192.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Tyr Lys Leu Cys               
His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro               
Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala               
Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly               
Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr               
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile               
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu               
Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu               
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu               
Lys Leu Cys Ala Thr (SEQ ID NO:176)                                       
13193.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Tyr Lys Leu Cys               
His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro               
Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala               
Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly               
Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr               
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile               
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu               
Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu               
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu               
Lys Leu Cys Ala Thr (SEQ ID NO:177)                                       
25190.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Pro Glu Leu Gly               
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr               
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu               
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr               
Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys               
Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu               
Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu               
Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu               
Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser               
Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala               
Leu Glu Gly Ile Ser (SEQ ID NO:178)                                       
pMON25191.Pep                                                             
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Pro Glu Leu Gly               
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr               
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu               
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr               
Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys               
Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu               
Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu               
Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu               
Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser               
Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala               
Leu Glu Gly Ile Ser (SEQ ID NO:179)                                       
13194.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Met Ala Pro Ala               
Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe               
Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser               
Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro               
Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu               
Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala               
Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu               
Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro               
Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu               
Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln               
Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr               
Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln               
Met Glu Glu Leu Gly (SEQ ID NO:180)                                       
13195.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Met Ala Pro Ala               
Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe               
Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser               
Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro               
Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu               
Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala               
Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu               
Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro               
Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu               
Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln               
Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr               
Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln               
Met Glu Glu Leu Gly (SEQ ID NO:181)                                       
13196.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Thr Gln Gly Ala               
Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val               
Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg               
Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu Gly Pro Ala Ser               
Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg               
Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala               
Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His               
Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln               
Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu               
Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro               
Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp               
Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala               
Pro Ala Leu Gln Pro (SEQ ID NO:182)                                       
13197.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala               
Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val               
Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg               
Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu Gly Pro Ala Ser               
Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg               
Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala               
Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His               
Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln               
Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu               
Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro               
Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp               
Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala               
Pro Ala Leu Gln Pro (SEQ ID NO:183)                                       
13198.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr               
Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys               
Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu               
Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu               
Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu               
Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser               
Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala               
Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu               
Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met               
Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala               
Met Pro Ala Phe Ala (SEQ ID NO:184)                                       
13199.Pept                                                                
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr               
Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys               
Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu               
Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu               
Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu               
Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser               
Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala               
Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu               
Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met               
Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala               
Met Pro Ala Phe Ala (SEQ ID NO:185)                                       
31104.Pep                                                                 
Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met               
Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala               
Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg               
Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg               
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu               
Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln               
Gln Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp Glu Ile Ile               
His His Leu Lys Arg Pro Pro Ala Pro Leu Tyr Val Glu Gly Gly               
Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn               
Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly               
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val               
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys               
Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly               
His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser               
Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly               
Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser               
Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala               
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met               
Ala Pro Ala Leu Gln Pro (SEQ ID NO:186)                                   
31105.Pep                                                                 
Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys               
Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile               
Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr               
Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser               
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Tyr Val Glu Gly Gly               
Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn               
Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly               
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val               
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys               
Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly               
His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser               
Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly               
Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser               
Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala               
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met               
Ala Pro Ala Leu Gln Pro (SEQ ID NO:187)                                   
31106.Pep                                                                 
Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln               
Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln               
Ala Gln Glu Gln Gln Gly Gly Gly Ser Asn Cys Ser Ile Met Ile               
Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu               
Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp               
Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val               
Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn               
Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Tyr Val Glu Gly Gly               
Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn               
Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly               
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val               
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys               
Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly               
His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser               
Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly               
Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser               
Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala               
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met               
Ala Pro Ala Leu Gln Pro (SEQ ID NO:188)                                   
31107.Pep                                                                 
Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu               
Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser Asn               
Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro               
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val               
Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser               
Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu               
Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala               
Ala Pro Ser Arg His Pro Ile Ile Ile Lys Thr Val Glu Gly Gly               
Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn               
Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly               
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val               
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys               
Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly               
His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser               
Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly               
Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser               
Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala               
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met               
Ala Pro Ala Leu Gln Pro (SEQ ID NO:189)                                   
31108.Pep                                                                 
Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met               
Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala               
Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg               
Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg               
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu               
Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln               
Gln Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Asn Cys               
Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro               
Ala Pro Leu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro               
Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu               
Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala               
Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala               
Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg               
His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe               
Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly               
Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His               
Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp               
Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly               
Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu               
Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu               
Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp               
Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro                   
(SEQ ID NO:190)                                                           
31109.Pep                                                                 
Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys               
Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile               
Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr               
Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp               
Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp               
Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp Arg               
Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys               
Asn Leu Glu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro               
Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu               
Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala               
Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala               
Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg               
His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe               
Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly               
Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His               
Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp               
Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly               
Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu               
Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu               
Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp               
Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro                   
(SEQ ID NO:191)                                                           
31110.Pep                                                                 
Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln               
Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln               
Ala Gln Glu Gln Gln Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly               
Gly Ser Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu               
Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp               
Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn               
Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser               
Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser               
Ala Thr Ala Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro               
Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu               
Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala               
Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala               
Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg               
His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe               
Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly               
Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His               
Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp               
Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly               
Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu               
Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu               
Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp               
Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro                   
(SEQ ID NO:192)                                                           
31111.Pep                                                                 
Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu               
Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser Gly               
Gly Gly Ser Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp Glu               
Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro               
Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn               
Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn               
Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln               
Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile               
Ile Ile Lys Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro               
Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu               
Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala               
Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala               
Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg               
His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe               
Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly               
Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His               
Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp               
Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly               
Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu               
Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu               
Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp               
Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro                   
(SEQ ID NO:193)                                                           
pMON15981                                                                 
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla              
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn              
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer              
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro              
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr              
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly              
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu              
SerHisLysSerProAsnMetAlaTyrLysLeuCysHisProGluGluLeuValLeuLeu              
GlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln              
LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln              
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVal              
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu              
GlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGly              
ValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHis              
LeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeu              
ProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAla              
AlaLeuGlnGluLysLeuCysAlaThr (SEQ ID NO:194)                               
pMON15982                                                                 
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla              
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn              
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer              
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro              
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr              
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly              
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu              
SerHisLysSerProAsnMetAlaProGluLeuGlyProThrLeuAspThrLeuGlnLeu              
AspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaPro              
AlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAla              
GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeu              
ArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSer              
SerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAsp              
GlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeu              
ValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGln              
AlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGly              
LeuLeuGlnAlaLeuGluGlyIleSer (SEQ ID NO:195)                               
pMON15965                                                                 
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla              
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn              
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer              
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro              
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr              
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly              
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu              
SerHisLysSerProAsnMetAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuVal              
AlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGln              
ProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSer              
PheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGln              
GluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHis              
SerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAla              
GlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeu              
GluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAsp              
PheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro              
ThrGlnGlyAlaMetProAlaPheAla (SEQ ID NO:196)                               
pMON15966                                                                 
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla              
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn              
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer              
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro              
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr              
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly              
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu              
SerHisLysSerProAsnMetAlaMetAlaProAlaLeuGlnProThrGlnGlyAlaMet              
ProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeu              
GlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGly              
SerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLys              
SerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCys              
AlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIle              
ProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSer              
GlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer              
ProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThr              
IleTrpGlnGlnMetGluGluLeuGly (SEQ ID NO:197)                               
pMON15967                                                                 
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla              
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn              
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer              
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro              
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr              
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly              
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu              
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe              
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer              
TyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeu              
GlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLys              
IleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHis              
ProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSer              
CysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPhe              
LeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeu              
AspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGlu              
LeuGlyMetAlaProAlaLeuGlnPro (SEQ ID NO:198)                               
pMON31112.pep                                                             
MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeu              
ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsn              
LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer              
AlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro              
ThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThr              
PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly              
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu              
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe              
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer              
TyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPhe              
LeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu              
LysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSer              
LeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGly              
CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGlu              
GlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPhe              
AlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro                 
(SEQ ID NO:199)                                                           
pMON31113.pep                                                             
MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeu              
ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsn              
LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer              
AlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro              
ThrArgHisProIleIleIleArgAspGlyAspTrpAsnGluPheArgArgLysLeuThr              
PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly              
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu              
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe              
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer              
TyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuPro              
GlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAla              
LeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeu              
GlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln              
LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln              
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVal              
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu              
GlnPro (SEQ ID NO:200)                                                    
pMON31114.pep                                                             
MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeu              
ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsn              
LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer              
AlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro              
ThrArgHisProIleIleIleArgAspGlyAspTrpAsnGluPheArgArgLysLeuThr              
PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly              
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu              
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe              
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer              
TyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPhe              
LeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu              
LysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSer              
LeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGly              
CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGlu              
GlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPhe              
AlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro                 
(SEQ ID NO:201)                                                           
pMON31115.pep                                                             
MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeu              
ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsn              
LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer              
AlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro              
ThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThr              
PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly              
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu              
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe              
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer              
TyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuPro              
GlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAla              
LeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeu              
GlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGluAlaLeuGln              
LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln              
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVal              
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu              
GlnPro (SEQ ID NO:202)                                                    
pMON28505                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGluAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetGluValHisProLeuProThrProValLeuLeuProAlaVal              
AspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGluAspIleLeu              
GlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThr              
CysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeu              
GlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspPro              
AsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeu              
ValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaPro              
ProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSer              
ArgLeuSerGlnCysPro (SEQ ID NO:203)                                        
pMON28506                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGluAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetLeuProThrProValLeuLeuProAlaValAspPheSerLeu              
GlyGluTrpLysThrGlnMetGluGluThrLysAlaGluAspIleLeuGlyAlaValThr              
LeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSer              
LeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeu              
GlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePhe              
LeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySer              
ThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAsp              
LeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGln              
CysProGluValHisPro (SEQ ID NO:204)                                        
pMON28507                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLys              
ThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGlu              
GlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGln              
LeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeu              
ProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGln              
HisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal              
ArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeu              
SerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluVal              
HisProLeuProThrPro (SEQ ID NO:205)                                        
pMON28508                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGluAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu              
GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla              
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln              
ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly              
ArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArg              
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly              
GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu              
ArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro              
ThrProValLeuLeuPro (SEQ ID NO:206)                                        
pMON28509                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGluAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThr              
LysAlaGluAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArg              
GlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArg              
LeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThr              
ThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLys              
ValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsn              
MetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAsp              
SerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro              
ValLeuLeuProAlaVal (SEQ ID NO:207)                                        
pMON28510                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAsp              
IleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGly              
ProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGly              
AlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys              
AspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu              
MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerPro              
AlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeu              
HisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuPro              
AlaValAspPheSerLeu (SEQ ID NO:208)                                        
pMON28511                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly              
GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln              
GlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeu              
ArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe              
GlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeu              
LeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeu              
ProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMet              
GluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMet              
AlaAlaArgGlyGlnLeu (SEQ ID NO:209)                                        
pMON28512                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys              
AspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu              
MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerPro              
AlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeu              
HisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuPro              
AlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAsp              
IleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGly              
ProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGly              
AlaLeuGlnSerLeuLeu (SEQ ID NO:210)                                        
pMON28513                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeu              
SerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThr              
LeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeu              
ArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCys              
ProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGly              
GluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeu              
LeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeu              
LeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGly              
ThrGlnLeuProProGln (SEQ ID NO:211)                                        
pMON28514                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis              
LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg              
GluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSer              
LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis              
ProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThr              
GlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGly              
ValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeu              
SerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuPro              
ProGlnGlyArgThrThr (SEQ ID NO:212)                                        
pMON28515                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArg              
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly              
GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu              
ArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro              
ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu              
GluThrLysAlaGluAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla              
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln              
ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly              
ArgThrThrAlaHisLys (SEQ ID NO:213)                                        
pMON28516                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysVal              
ArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMet              
AlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer              
HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVal              
LeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLys              
AlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGly              
GlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeu              
LeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThr              
AlaHisLysAspProAsn (SEQ ID NO:214)                                        
pMON28519                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetGluValHisProLeuProThrProValLeuLeuProAlaVal              
AspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeu              
GlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThr              
CysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeu              
GlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspPro              
AsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeu              
ValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProPro              
AlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArg              
LeuSerGlnCysPro (SEQ ID NO:215)                                           
pMON28520                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetLeuProThrProValLeuLeuProAlaValAspPheSerLeu              
GlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThr              
LeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSer              
LeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeu              
GlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePhe              
LeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySer              
ThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeu              
ArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCys              
ProGluValHisPro (SEQ ID NO:216)                                           
pMON28521                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLys              
ThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGlu              
GlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGln              
LeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeu              
ProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGln              
HisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal              
ArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSer              
LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis              
ProLeuProThrPro (SEQ ID NO:217)                                           
pMON28522                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu              
GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla              
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln              
ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly              
ArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArg              
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly              
AsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArg              
AspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThr              
ProValLeuLeuPro (SEQ ID NO:218)                                           
pMON28523                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGluAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThr              
LysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArg              
GlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArg              
LeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThr              
ThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLys              
ValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMet              
AlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer              
HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVal              
LeuLeuProAlaVal (SEQ ID NO:219)                                           
pMON28524                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGluAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAsp              
IleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGly              
ProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGly              
AlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys              
AspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu              
MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAla              
ProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHis              
SerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAla              
ValAspPheSerLeu (SEQ ID NO:220)                                           
pMON28525                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly              
GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln              
GlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeu              
ArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe              
GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu              
ArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro              
ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu              
GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla              
AlaArgGlyGlnLeu (SEQ ID NO:221)                                           
pMON28526                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys              
AspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu              
MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAla              
ProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHis              
SerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAla              
ValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIle              
LeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyPro              
ThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAla              
LeuGlnSerLeuLeu (SEQ ID NO:222)                                           
pMON28527                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeu              
SerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThr              
LeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArg              
ValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysPro              
GluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGlu              
TrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeu              
LeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeu              
GlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThr              
GlnLeuProProGln (SEQ ID NO:223)                                           
pMON28528                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis              
LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg              
GluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLys              
LeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisPro              
LeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGln              
MetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyVal              
MetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSer              
GlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProPro              
GlnGlyArgThrThr (SEQ ID NO:224)                                           
pMON28529                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArg              
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly              
AsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArg              
AspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThr              
ProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu              
ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAla              
ArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnVal              
ArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArg              
ThrThrAlaHisLys (SEQ ID NO:225)                                           
pMON28530                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGluAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysVal              
ArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAla              
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis              
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu              
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla              
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln              
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu              
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla              
HisLysAspProAsn (SEQ ID NO:226)                                           
pMON28533                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetGluValHisProLeuProThrProValLeuLeuProAlaVal              
AspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeu              
GlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThr              
CysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeu              
GlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspPro              
AsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeu              
ValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSer              
ProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisVal              
LeuHisSerArgLeuSerGlnCysPro (SEQ ID NO:227)                               
pMON28534                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetLeuProThrProValLeuLeuProAlaValAspPheSerLeu              
GlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThr              
LeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSer              
LeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeu              
GlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePhe              
LeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySer              
ThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProPro              
AlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArg              
LeuSerGlnCysProGluValHisPro (SEQ ID NO:228)                               
pMON28535                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLys              
ThrGlnMetGluGluThrLysAlaGluAspIleLeuGlyAlaValThrLeuLeuLeuGlu              
GlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGln              
LeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeu              
ProProGlnGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGln              
HisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal              
ArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeu              
ArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCys              
ProGluValHisProLeuProThrPro (SEQ ID NO:229)                               
pMON28536                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGluAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu              
GluThrLysAlaGluAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla              
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln              
ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly              
ArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArg              
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly              
GlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSer              
LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis              
ProLeuProThrProValLeuLeuPro (SEQ ID NO:230)                               
pMON28537                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThr              
LysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArg              
GlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArg              
LeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThr              
ThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLys              
ValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsn              
GlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeu              
LeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeu              
ProThrProValLeuLeuProAlaVal (SEQ ID NO:231)                               
pMON28538                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPh&ArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGluAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetGlyGluTrpLysThrGlnMetGluGluThrLysAlaGluAsp              
IleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGly              
ProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGly              
AlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys              
AspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu              
MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMet              
AlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer              
HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVal              
LeuLeuProAlaValAspPheSerLeu (SEQ ID NO:232)                               
pMON28539                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGluAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly              
GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln              
GlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeu              
ArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe              
GlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeu              
SerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluVal              
HisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLys              
ThrGlnMetGluGluThrLysAlaGluAspIleLeuGlyAlaValThrLeuLeuLeuGlu              
GlyValMetAlaAlaArgGlyGlnLeu (SEQ ID NO:233)                               
pMON28540                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys              
AspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu              
MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMet              
AlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer              
HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVal              
LeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLys              
AlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGly              
GlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeu              
LeuLeuGlyAlaLeuGlnSerLeuLeu (SEQ ID NO:234)                               
pMON28541                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeu              
SerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThr              
LeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAla              
CysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeu              
SerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPhe              
SerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAla              
ValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeu              
SerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSer              
LeuLeuGlyThrGlnLeuProProGln (SEQ ID NO:235)                               
pMON28542                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis              
LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg              
GluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArg              
ValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysPro              
GluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGlu              
TrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeu              
LeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeu              
GlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThr              
GlnLeuProProGlnGlyArgThrThr (SEQ ID NO:236)                               
pMON28543                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGluAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArg              
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly              
GlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSer              
LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis              
ProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThr              
GlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGly              
ValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeu              
SerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuPro              
ProGlnGlyArgThrThrAlaHisLys (SEQ ID NO: 237)                              
pMON28544                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysVal              
ArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGly              
GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu              
ArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro              
ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu              
GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla              
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln              
ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly              
ArgThrThrAlaHisLysAspProAsn (SEQ ID NO: 238)                              
pMON28545                                                                 
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro              
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu              
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly              
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer              
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe              
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer              
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer              
HisLysSerProAsnMetAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArg              
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly              
GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu              
ArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro              
ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu              
GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla              
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln              
ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnGlyArgThrThrAla              
HisLys (SEQ ID NO:239)                                                    
pMON32132                                                                 
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis              
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu              
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla              
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln              
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu              
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla              
HisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg              
PheLeuMetLeuValGlyGlySerThrLeuCysValArg (SEQ ID NO: 252)                  
PMON32133                                                                 
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis              
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu              
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla              
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln              
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu              
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnGlyArgThrThrAlaHisLysAspPro              
AsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeu              
ValGlyGlySerThrLeuCysValArg (SEQ ID NO:253)                               
PMON32134                                                                 
SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis              
ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu              
LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla              
GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln              
LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu              
LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla              
HisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg              
PheLeuMetLeuValGlyGlySerThrLeuCysValArg (SEQ ID NO:254)                   
pmon16017.pep                                                             
  1                                                                       
  Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu             
 16                                                                       
   Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp            
 31                                                                       
   Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn            
 46                                                                       
   Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser            
 61                                                                       
   Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser            
 76                                                                       
   Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly            
 91                                                                       
   Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr            
106                                                                       
   Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly            
121                                                                       
   Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser            
136                                                                       
   Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Leu Gly            
151                                                                       
   Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu            
166                                                                       
   Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys            
181                                                                       
   Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu            
196                                                                       
   Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys            
211                                                                       
   Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His            
226                                                                       
   Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly            
241                                                                       
   Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp            
256                                                                       
   Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu            
271                                                                       
   Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala            
286                                                                       
   Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala            
301                                                                       
   Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg            
316                                                                       
   His Leu Ala Gln Pro Asp Met Ala Thr Pro (SEQ ID NO:271)                
pmon16018.pep                                                             
  1                                                                       
  Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu             
 16                                                                       
   Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp            
 31                                                                       
   Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn            
 46                                                                       
   Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser            
 61                                                                       
   Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser            
 76                                                                       
  Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly             
 31                                                                       
  Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr             
106                                                                       
  Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly             
121                                                                       
  Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser             
136                                                                       
  Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Leu Gly             
151                                                                       
  Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu             
176                                                                       
  Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys             
191                                                                       
  Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu             
206                                                                       
  Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys             
221                                                                       
  Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His             
236                                                                       
  Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly             
251                                                                       
  Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp             
266                                                                       
  Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu             
281                                                                       
  Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala             
296                                                                       
  Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala             
311                                                                       
  Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg             
326                                                                       
  His Leu Ala Gln Pro Asp Met Ala Thr Pro (SEQ ID NO:272)                 
pmon16019.pep                                                             
  1                                                                       
  Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu             
 16                                                                       
  Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp             
 31                                                                       
  Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn             
 46                                                                       
  Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser             
 61                                                                       
  Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser             
 76                                                                       
  Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly             
 91                                                                       
  Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr             
106                                                                       
  Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly             
121                                                                       
  Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser             
136                                                                       
  Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Phe Leu             
151                                                                       
  Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala             
166                                                                       
  Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro             
181                                                                       
  Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala             
196                                                                       
  Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys             
211                                                                       
  Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu             
226                                                                       
  Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp             
241                                                                       
  Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln             
256                                                                       
  Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln             
271                                                                       
  Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly             
286                                                                       
  Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser             
301                                                                       
  Tyr Arg Val Leu Arg His Leu Ala Gln Pro Asp Met Ala Thr Pro             
316                                                                       
  Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser (SEQ ID NO:273)                 
pmon16020.pep                                                             
  1                                                                       
  Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu             
 16                                                                       
  Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp             
 31                                                                       
  Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn             
 46                                                                       
  Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser             
 61                                                                       
  Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser             
 76                                                                       
  Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly             
 91                                                                       
  Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr             
106                                                                       
  Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly             
121                                                                       
  Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser             
136                                                                       
  Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Glu Gln             
151                                                                       
  Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu             
166                                                                       
  Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu             
181                                                                       
  Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro             
196                                                                       
  Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser             
211                                                                       
  Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile             
226                                                                       
  Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val             
241                                                                       
  Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly             
256                                                                       
  Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe             
271                                                                       
  Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser             
286                                                                       
  His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His             
301                                                                       
  Leu Ala Gln Pro Asp Met Ala Thr Pro Leu Gly Pro Ala Ser Ser             
316                                                                       
  Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu (SEQ ID NO:274)                 
pmon16021.pep                                                             
  1 Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu           
 16 Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp           
 31 Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn           
 46 Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser           
 61 Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser           
 76 Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly           
 91 Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr           
106 Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly           
121 Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser           
136 Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Leu Leu           
151 Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro           
166 Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser           
181 Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile           
196 Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val           
211 Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly           
226 Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe           
241 Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser           
256 His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His           
271 Leu Ala Gln Pro Asp Met Ala Thr Pro Leu Gly Pro Ala Ser Ser           
286 Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys           
301 Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr           
316 Tyr Lys Leu Cys His Pro Glu Glu Leu Val (SEQ ID NO:275)               
pmon16022.pep                                                             
  1 Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu           
 16 Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp           
 31 Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn           
 46 Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser           
 61 Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser           
 76 Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly           
 91 Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr           
106 Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly           
121 Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser           
136 Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Pro Leu           
151 Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser           
166 Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala           
181 Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu           
196 Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met           
211 Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala           
226 Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val           
241 Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg           
256 Val Leu Arg His Leu Ala Gln Pro Asp Met Ala Thr Pro Leu Gly           
271 Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu           
286 Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys           
301 Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu           
316 Leu Gly His Ser Leu Gly Ile Pro Trp Ala (SEQ ID NO:276)               
pmon16023.pep                                                             
  1                                                                       
  Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu             
 16                                                                       
   Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp            
 31                                                                       
   Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn            
 46                                                                       
   Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser            
 61                                                                       
   Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser            
 76                                                                       
   Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly            
 91                                                                       
   Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr            
106                                                                       
   Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly            
121                                                                       
   Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser            
136                                                                       
   Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Gln Ala            
151                                                                       
   Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe            
166                                                                       
   Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu            
181                                                                       
   Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe            
196                                                                       
   Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro            
211                                                                       
   Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala            
226                                                                       
   Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln            
241                                                                       
   Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln            
256                                                                       
   Pro Asp Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln            
271                                                                       
   Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly            
286                                                                       
   Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu            
301                                                                       
   Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile            
316                                                                       
   Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser (SEQ ID NO:277)                
pmon16024.pep                                                             
  1                                                                       
  Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu             
 16                                                                       
   Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp            
 31                                                                       
   Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn            
 46                                                                       
   Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser            
 61                                                                       
   Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser            
 76                                                                       
   Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly            
 91                                                                       
   Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr            
106                                                                       
   Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly            
121                                                                       
   Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser            
136                                                                       
   Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Leu Gln            
151                                                                       
   Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr            
166                                                                       
   Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly            
181                                                                       
   Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr            
196                                                                       
   Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu            
211                                                                       
   Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln            
226                                                                       
   Arg Arg Ala Gly Gly Valleu Val Ala Ser His Leu Gln Ser Phe             
241                                                                       
   Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Asp            
256                                                                       
   Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe            
271                                                                       
   Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly            
286                                                                       
   Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His            
301                                                                       
   Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp            
316                                                                       
   Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala (SEQ ID NO:278)                
pmon16025.pep                                                             
  1                                                                       
  Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu             
 16                                                                       
   Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp            
 31                                                                       
   Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn            
 46                                                                       
   Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser            
 61                                                                       
   Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser            
 76                                                                       
   Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly            
 91                                                                       
  Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr             
106                                                                       
  Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly             
121                                                                       
  Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser             
136                                                                       
  Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Leu Ala             
151                                                                       
  Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly             
166                                                                       
  Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr             
181                                                                       
  Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile             
196                                                                       
  Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro             
211                                                                       
  Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg             
226                                                                       
  Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu             
241                                                                       
  Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Asp Met Ala             
256                                                                       
  Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu             
271                                                                       
  Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala             
286                                                                       
  Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu             
301                                                                       
  Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro             
316                                                                       
  Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln (SEQ ID NO:279)                 
pmon16026.pep                                                             
  1                                                                       
  Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu             
 16                                                                       
  Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp             
 31                                                                       
  Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn             
 46                                                                       
  Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser             
 61                                                                       
  Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser             
 76                                                                       
  Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly             
 91                                                                       
  Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr             
106                                                                       
  Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly             
121                                                                       
  Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser             
136                                                                       
  Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Glu Leu             
151                                                                       
  Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala             
166                                                                       
  Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala             
181                                                                       
  Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg             
196                                                                       
  His Leu Ala Gln Pro Asp Met Ala Thr Pro Leu Gly Pro Ala Ser             
211                                                                       
  Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg             
226                                                                       
  Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala             
241                                                                       
  Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His             
256                                                                       
  Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln             
271                                                                       
  Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu             
286                                                                       
  Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro             
301                                                                       
  Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp             
316                                                                       
  Phe Ala Thr Thr Ile Trp Gln Gln Met Glu (SEQ ID NO:280)                 
pmon16027.pep                                                             
  1                                                                       
  Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu             
 16                                                                       
  Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp             
 31                                                                       
  Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn             
 46                                                                       
  Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser             
 61                                                                       
  Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser             
 76                                                                       
  Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly             
 91                                                                       
  Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr             
106                                                                       
  Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly             
121                                                                       
  Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser             
136                                                                       
  Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Gly Met             
151                                                                       
  Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala             
166                                                                       
  Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His             
181                                                                       
  Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu             
196                                                                       
  Ala Gln Pro Asp Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu             
211                                                                       
  Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile             
226                                                                       
   Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr            
241                                                                       
   Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu            
256                                                                       
   Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu            
271                                                                       
   Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu            
286                                                                       
   Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu            
301                                                                       
   Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala            
316                                                                       
   Thr Thr Ile Trp Gln Gln Met Glu Glu Leu (SEQ ID NO:281)                
pmon16028.pep                                                             
  1                                                                       
  Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu             
 16                                                                       
   Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp            
 31                                                                       
   Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn            
 46                                                                       
   Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser            
 61                                                                       
   Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser            
 76                                                                       
   Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly            
 91                                                                       
   Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr            
106                                                                       
   Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly            
121                                                                       
   Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser            
136                                                                       
   Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Ser Phe            
151                                                                       
   Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Asp            
166                                                                       
   Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe            
181                                                                       
   Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly            
196                                                                       
   Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His            
211                                                                       
   Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp            
226                                                                       
   Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly            
241                                                                       
   Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu            
256                                                                       
   Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu            
271                                                                       
   Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp            
286                                                                       
   Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr            
301                                                                       
   Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala            
316                                                                       
   Gly Gly Val Leu Val Ala Ser His Leu Gln (SEQ ID NO:282)                
MetAlaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis              
LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuAlaValArg              
GluPheGlyGlyAsnMetAlaSerProAlaProProAlaAlaAspLeuArgValLeuSer              
LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis              
ProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThr              
GlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGly              
ValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeu              
SerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuPro              
ProGln (SEQ ID NO:284);                                                   
MetAlaGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeu              
LeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThr              
AlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysVal              
ArgPheLeuMetLeuValGlyGlySerThrLeuAlaValArgGluPheGlyGlyAsnMet              
AlaSerProAlaProProAlaAlaAspLeuArgValLeuSerLysLeuLeuArgAspSer              
HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVal              
LeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLys              
AlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGly              
GlnLeu (SEQ ID NO:285)                                                    
__________________________________________________________________________
The following examples will illustrate the invention in greater detail although it will be understood that the invention is not limited to these specific examples.
EXAMPLE 1 Construction of Parental BHK Expression Vector
A. Removal of AflIII site from mammalian expression plasmid.
A new mammalian expression vector was constructed to accept NcoI-HindIII or AflIII-HindIII gene fragments in-frame and 3' to the hIL-3 receptor agonist pMON13146 (WO 94/12638) gene and a mouse IgG2b linker fragment. First, the single AflIII site was removed from pMON3934, which is a derivative of pMON3359. pMON3359 is a pUC18-based vector containing a mammalian expression cassette. The cassette includes a herpes simplex viral promoter IE110 (-800 to +120) followed by a modified human IL-3 signal peptide sequence and an SV40 late poly-adenylation (poly-A) signal which has been subcloned into the pUC18 polylinker (See Hippenmeyer et al., Bio/Technology, 1993, pp.1037-1041). The modified human IL-3 signal sequence, which facilitates secretion of gene products outside of the cell, is flanked by a BamHI site on the 5' end and a unique NcoI site on the 3' end. A unique HindIII site is 3' to the NcoI site and 5' to the poly-A sequence. The DNA sequence encoding the signal peptide is shown below (restriction enzyme sites are indicated above). The ATG (methionine) codon within the NcoI site is in-frame with the initiator ATG of the signal peptide (underlined); BamHI NcoI 5'GGATCCACCATGAGCCTGCCCGTCCTGCTCCTGCTCCAACTCCTGGTCCGCCCCGCCATGG (SEQ ID NO:255)
The single AflIII site was removed from pMON3934 by digestion with AflIII followed by filling in the overhangs by addition of a DNA polymerase and nucleotides. The digested DNA fragment was purified via Magic PCR Clean up kit (Promega) and ligated with T4 DNA ligase. The ligation reaction was transformed into DH5α ™ and the cells were plated onto LB-agar plus ampicillin. Individual colonies were screened for the loss of the AflIII site by restriction analysis with AflIII and HindIII which results in a single fragment if the AflIII site was removed. The resulting plasmid was designated pMON30275.
B. Transfer of hIL-3 receptor agonist pMON13416/IgG2b cassette into pMON30275.
The NcoI-HindIII fragment (ca. 425 bp) from pMON30245 was ligated to the NcoI-HindIII fragment (ca. 3800 bp) of the pMON30275. pMON30245 (WO 94/12638) contains the gene coding for hIL-3 receptor agonist pMON13416 joined to a mouse IgG2b hinge fragment. Immediately 3' to the IgG2b hinge and 5' to the HindIII site is an AflIII site. Genes can be cloned into the AflIII-HindIII sites as NcoI-HindIII or AflIII-HindIII fragments in frame with the hIL-3 variant pMON13416/IgG2b hinge to create novel chimeras. The NcoI site and the AflIII site have compatible overhangs and will ligate but both recognition sites are lost. The plasmid, pMON30304 containing the DNA sequence of (SEQ ID NO:78), coding for hIL-3 variant pMON13416 joined with a mouse IgG2b hinge region, was a result of this cloning.
EXAMPLE 2
Construction of an intermediate plasmid containing one copy of the c-mpl ligand (1-153) gene of the dimer template
In order to generate a plasmid DNA with the coding sequence of c-mpl (1-153) ligand followed by a unique EcoRI restriction site, the gene is isolated via reverse transcriptase/polymerase chain reaction (RT/PCR). Human fetal (lot #38130) and adult liver (lot #46018) A+RNA are obtained from Clontech (Palo Alto, Calif.) for source of c-mpl ligand messenger RNA (mRNA). The first strand cDNA reactions are carried out using a cDNA Cycle™ Kit obtained from Invitrogen (San Diego, Calif.). In the RT reaction, random primers and oligo dT primer are used to generate cDNA from a combination of human and fetal liver mRNA. For amplification of c-mpl ligand gene fragment encoding amino acids 1-153, the RT product serves as the template for PCR with a combination of the primers, Forward primer: c-mplNcoI (SEQ ID NO:13) and Reverse primer: Ecompl. The c-mplNcoI primer anneals to the c-mpl ligand gene (bases #279-311 based on c-mpl ligand sequence from Gene bank accession #L33410 or de Sauvage et al., Nature 369: 533-538 (1994)) and encodes a NcoI restriction enzyme site immediately 5' to the first codon (Ser+1) of c-mpl ligand. The NcoI restriction enzyme site codes for methionine and alanine codons prior to Ser+1 and includes codon degeneracy for the Ala codon and the first four codons (Ser, Pro, Ala, & Pro) of c-mpl ligand. The Ecompl primer anneals to bases #720-737 of c-mpl ligand and encodes an EcoRI site (GAATTC) in-frame with the c-mpl ligand gene immediately following Arg-153. The EcoRI site creates Glu and Phe codons following Arg-153. The ca. 480 bp PCR product was purified, digested with NcoI and EcoRI and ligated to the NcoI-EcoRI vector fragment of pMON3993 (ca. 4550 bp.). pMON3993 was a derivative of pMON3359 (described in Example 1). The human IL-3 signal peptide sequence, which had been subcloned as a BamHI fragment into the unique BamHI site between the IE110 promoter and poly-A signal, contains an NcoI site at its 3' end and is followed by a unique EcoRI site. The plasmid, pMON26458 containing the DNA sequence of (SEQ ID NO:79), coding for c-mpl ligand amino acids 1-153 (SEQ ID NO:161), was the result of this cloning.
EXAMPLE 3
Construction of the parental plasmids containing the second genes of the dimer templates
For amplification of c-mpl ligand gene fragments starting at amino acid 1 (Ser) with a termination codon following amino acid 153 (Arg), the RT reaction from Example 2 serves as the template for PCR with a combination of the following primers; c-mplNcoI (SEQ ID NO:13) (forward primer) and c-mplHindIII (SEQ ID NO:15) (reverse primer). The c-mplNcoI (SEQ ID NO:13) primer is described in Example 2. The c-mplHindIII (SEQ ID NO:15) primer, which anneals to bases #716-737 of c-mpl ligand, adds both a termination codon and a HindIII restriction enzyme site immediately following the final codon, Arg153.
Two types of PCR products are generated from the RT cDNA samples, one with a deletion of the codons for amino acids 112-115 and one without the deletion of these codons. The c-mpl ligand PCR products (ca. 480 bp) are digested with NcoI and HindIII restriction enzymes for transfer to a mammalian expression vector, pMON3934. pMON3934 is digested with NcoI and HindIII (ca. 3800 bp) and will accept the PCR products.
Plasmid, pMON32132 (SEQ ID NO:249), coding for c-mpl ligand amino acids 1-153 (SEQ ID NO:252) was a result of this cloning. Plasmid, pMON32134 (SEQ ID NO:250), coding for c-mpl ligand amino acids 1-153 (SEQ ID NO:253) was a result of this cloning. Plasmid, pMON32133 (SEQ ID NO:251), coding for c-mpl ligand amino acids 1-153 with a deletion of codons 112-115 (Δ112-115) (SEQ ID NO:254) was also a result of this cloning.
EXAMPLE 4
Generation of PCR dimer template 5L with a Δ112-115 deletion in the second c-mpl ligand gene
A PCR template for generating novel forms of c-mpl ligand is constructed by ligating the 3.7 Kbp BstXI/EcoRI fragment of pMON26458 to the 1 Kbp NcoI/BstXI fragment from pMON32133 (containing a deletion of amino acids 112-115) along with the EcoRI/AflIII 5L synthetic oligonucleotide linker 5L-5' (SEQ ID NO:18) and 5L-3' (SEQ ID NO:19).
The EcoRI end of the linker will ligate to the EcoRI end of pMON26458. The AflIII end of the linker will ligate to the NcoI site of pMON32133, and neither restriction site will be retained upon ligation. The BstXI sites of pMON26458 and pMON32133 will ligate as well. Plasmid, pMON28548, is a result of the cloning and contains the DNA sequence of (SEQ ID NO:80) which encodes amino acids 1-153 c-mpl ligand fused via a GluPheGlyGlyAsnMetAla (SEQ ID NO:222) linker to amino acids 1-153 c-mpl ligand that contains a deletion of amino acids 112-115 (SEQ ID NO:162).
EXAMPLE 5 Generation of PCR Dimer Template 4L
A PCR template for generating novel forms of c-mpl ligand is constructed by ligating the 3.7 Kbp BstXI/EcoRI fragment of pMON26458 to the 1 Kbp NcoI/BstXI fragment from pMON32132 along with the EcoRI/AflIII 4L synthetic oligonucleotide linker 4L-5' (SEQ ID NO:16) and 4L-3' (SEQ ID NO:17).
The EcoRI end of the linker will ligate to the EcoRI end of pMON26458. The AflIII end of the linker will ligate to the NcoI site of pMON32132, and neither restriction site will be retained upon ligation. The BstXI sites of pMON26458 and pMON32132 will ligate as well. The plasmid, pMON28500, is a result of the cloning and contains the DNA sequence of (SEQ ID NO:82) which encodes amino acids 1-153 c-mpl ligand fused via a GluPheGlyAsnMetAla (SEQ ID NO:223) linker (4L) to amino acids 1-153 c-mpl ligand (SEQ ID NO:163).
EXAMPLE 6 Generation of PCR Dimer Template 5L
A PCR template for generating novel forms of c-mpl ligand is constructed by ligating the 3.7 Kbp BstXI/EcoRI fragment of pMON26458 to the 1 Kbp NcoI/BstXI fragment from pMON32132 along with the EcoRI/AflIII 5L synthetic oligonucleotide linker 5L-5' (SEQ ID NO:18) and 5L-3' (SEQ ID NO:19).
The EcoRI end of the linker will ligate to the EcoRI end of pMON26458. The AflIII end of the linker will ligate to the NcoI site of pMON32132, and neither restriction site will be retained upon ligation. The BstXI sites of pMON26458 and pMON32132 will ligate as well. Plasmid, pMON28501 is a result of the cloning and contains the DNA sequence of (SEQ ID NO: 82) which encodes amino acids 1-153 c-mpl ligand fused via a GluPheGlyGlyAsnMetAla (SEQ ID NO:222) linker (5L) to amino acids 1-153 c-mpl ligand (SEQ ID NO:164).
EXAMPLE 7 Generation of PCR Dimer Templates 8L
A PCR template for generating novel forms of c-mpl ligand is constructed by ligating the 3.7 Kbp BstXI/EcoRI fragment of pMON26458 to the 1 Kbp NcoI/BstXI fragment from pMON32134 along with the EcoRI/AflIII 8L synthetic oligonucleotide linker 8L-5' (SEQ ID NO:20) and 8L-3' (SEQ ID NO:21).
The EcoRI end of the linker will ligate to the EcoRI end of pMON26458. The AflIII end of the linker will ligate to the NcoI site of pMON32134, and neither restriction site will be retained upon ligation. The BstXI sites of pMON26458 and pMON32134 will ligate as well. Plasmid, pMON28502 is a result of the cloning which contains the DNA sequence of (SEQ ID NO:83) and encodes amino acids 1-153 c-mpl ligand fused via a GluPheGlyGlyAsnGlyGlyAsnMetAla (SEQ ID NO:224) linker (8L) to amino acids 1-153 c-mpl ligand (SEQ ID NO:165).
EXAMPLES 8-44
Generation of novel c-mpl ligand genes with new N-terminus and C-terminus
A. PCR generation of genes encoding novel c-mpl ligand receptor agonists.
Genes encoding novel c-mpl ligand receptor agonists were generated using Method III (Horlick et al., Prot. Eng. 5:427-433, 1992). The PCR reactions were carried out using dimer templates, pMONs 28500, 28501, 28502 or 28548 and one of the sets of synthetic primer sets below (The first number refers to the position of the first amino acid in the original sequence. For example, the 31-5' and 31-3' refers to the 5' and 3' oligo primers, receptively, for the sequence beginning at the codon corresponding to residue 31 of the original sequence.).
31-5' (SEQ ID NO:22) and 31-3' (SEQ ID NO:23), 35-5' (SEQ ID NO:24) and 35-3' (SEQ ID NO:25), 39-5' (SEQ ID NO:26) and 39-3' (SEQ ID NO:27), 43-5' (SEQ ID NO:28) and 43-3' (SEQ ID NO:29), 45-5' (SEQ ID NO:30) and 45-3' (SEQ ID NO:31), 49-5' (SEQ ID NO:32) and 49-3' (SEQ ID NO:33), 82-5' (SEQ ID NO:34) and 82-3' (SEQ ID NO:35), 109-5' (SEQ ID NO:36) and 109-3' (SEQ ID NO:37), 115-5' (SEQ ID NO:38) and 115-3' (SEQ ID NO:39), 120-5' (SEQ ID NO:40) and 120-3' (SEQ ID NO:41), 123-5' (SEQ ID NO:42) and 123-3' (SEQ ID NO:43), 126-5' (SEQ ID NO:44) and 126-3' (SEQ ID NO:45).
The templates and oligonucleotide sets used in the PCR reactions are shown in Table 4. The products that were generated were about 480 bp and were purified via Magic PCR Clean up kits (Promega).
B. Subcloning of novel c-mpl receptor agonist gene products into mammalian expression vector for generation of chimeras.
The c-mpl receptor agonist gene PCR products were digested with NcoI and HindIII or AflIII and HindIII restriction enzymes (ca. 470 bp) for transfer to a mammalian expression vector. The expression vector, pMON30304, was digested with NcoI and HindIII (ca. 4200 bp) and accepts the PCR products as NcoI-HindIII or AflIII-HindIII fragments. The restriction digest of the PCR product and the resulting plasmids are shown in Table 4.
                                  TABLE 4                                 
__________________________________________________________________________
                    PCR Product                                           
                               Resulting                                  
                                    Breakpoint                            
              PCR Product                                                 
                    Restriction                                           
                               Plasmid                                    
                                    in c-mpl                              
Example #                                                                 
       PCR template                                                       
              Primer set                                                  
                    Digest Linker                                         
                               pMON ligand                                
__________________________________________________________________________
Example 8                                                                 
       pMON28501                                                          
              31    NcoI/HindIII                                          
                           5L  28505                                      
                                    30-31                                 
Example 9                                                                 
        pMON28501                                                         
                        AflIII/HindIII                                    
                                    28506                                 
                                         34-35                            
Example 10                                                                
        pMON28501                                                         
                          NcoI/HindIII                                    
                                    28507                                 
                                         38-39                            
Example 11                                                                
        pMON28501                                                         
                          NcoI/HindIII                                    
                                    28508                                 
                                         42-43                            
Example 12                                                                
        pMON28501                                                         
                          NcoI/HindIII                                    
                                    28509                                 
                                         44-45                            
Example 13                                                                
        pMON28501                                                         
                          NcoI/HindIII                                    
                                    28510                                 
                                         48-49                            
Example 14                                                                
        pMON28501                                                         
                          NcoI/HindIII                                    
                                    28511                                 
                                         81-82                            
Example 15                                                                
        PMON28501                                                         
                    109                                                   
                          NcoI/HindIII                                    
                                    28512                                 
                                        108-109                           
Example 16                                                                
        PMON28501                                                         
                    116                                                   
                          NcoI/HindIII                                    
                                    28513                                 
                                        115-116                           
Example 17                                                                
        pMON28501                                                         
                    120                                                   
                          NcoI/HindIII                                    
                                    28514                                 
                                        119-120                           
Example 18                                                                
        pMON28501                                                         
                    123                                                   
                          NcoI/HindIII                                    
                                    28515                                 
                                        122-123                           
Example 19                                                                
        PMON28501                                                         
                    126                                                   
                          NcoI/HindIII                                    
                                    28516                                 
                                        125-126                           
Example 20                                                                
        pMON28500                                                         
                          NcoI/HindIII                                    
                                    28519                                 
                                         30-31                            
Example 21                                                                
        pMON28500                                                         
                        AflIII/HindIII                                    
                                    28520                                 
                                         34-35                            
Example 22                                                                
        pMON28500                                                         
                          NcoI/HindIII                                    
                                    28521                                 
                                         38-39                            
Example 23                                                                
        pMON28500                                                         
                          NcoI/HindIII                                    
                                    28522                                 
                                         42-43                            
Example 24                                                                
        pMON28500                                                         
                          NcoI/HindIII                                    
                                    28523                                 
                                         44-45                            
Example 25                                                                
        pMON28500                                                         
                          NcoI/HindIII                                    
                                    28524                                 
                                         48-49                            
Example 26                                                                
        PMON28500                                                         
                          NcoI/HindIII                                    
                                    28525                                 
                                         81-82                            
Example 27                                                                
        pMON28500                                                         
                    109                                                   
                          NcoI/HindIII                                    
                                    28526                                 
                                        108-109                           
Example 28                                                                
        pMON28500                                                         
                    116                                                   
                          NcoI/HindIII                                    
                                    28527                                 
                                        115-116                           
Example 29                                                                
        pMON28500                                                         
                    120                                                   
                          NcoI/HindIII                                    
                                    28528                                 
                                        119-120                           
Example 30                                                                
        pMON28500                                                         
                    123                                                   
                          NcoI/HindIII                                    
                                    28529                                 
                                        122-123                           
Example 31                                                                
        pMON28500                                                         
                    126                                                   
                          NcoI/HindIII                                    
                                    28530                                 
                                        125-126                           
Example 32                                                                
        pMON28502                                                         
                          NcoIIHindIII                                    
                                    28533                                 
                                         30-31                            
Example 33                                                                
        pMON28502                                                         
                        AflIII/HindIII                                    
                                    28534                                 
                                         34-35                            
Example 34                                                                
        pMON28502                                                         
                          NcoI/HindIII                                    
                                    28535                                 
                                         38-39                            
Example 35                                                                
        pMON28502                                                         
                          NcoI/HindIII                                    
                                    28536                                 
                                         42-43                            
Example 36                                                                
         pMON28502                                                        
                    45                                                    
                          NcoI/HindIII                                    
                               8L                                         
                                    28537                                 
                                          44-45                           
Example 37                                                                
         pMON28502                                                        
                    49                                                    
                          NcoI/HindIII                                    
                               8L                                         
                                    28538                                 
                                          48-49                           
Example 38                                                                
         pMON28502                                                        
                    82                                                    
                          NcoI/HindIII                                    
                               8L                                         
                                    28539                                 
                                          81-82                           
Example 39                                                                
        pMON28502                                                         
                   109                                                    
                          NcoI/HindIII                                    
                               8L                                         
                                    28540                                 
                                         108-109                          
Example 40                                                                
         pMON28502                                                        
                   116                                                    
                          NcoI/HindIII                                    
                               8L                                         
                                    28541                                 
                                         115-116                          
EXAMPLE 41                                                                
         pMON28502                                                        
                   120                                                    
                          NcoI/HindIII                                    
                               8L                                         
                                    28542                                 
                                         119-120                          
Example 42                                                                
         pMON28502                                                        
                   123                                                    
                          NcoI/HindIII                                    
                               8L                                         
                                    28543                                 
                                         122-123                          
Example 43                                                                
         pMON28502                                                        
                   126                                                    
                          NcoI/HindIII                                    
                               8L                                         
                                    28544                                 
                                         125-126                          
Example 44                                                                
         pMON28548                                                        
                   123                                                    
                          NcoI/HindIII                                    
                               5L                                         
                                    28545                                 
                                         122-123                          
__________________________________________________________________________
EXAMPLE 45 Construction of pMON15960
Construction of pMON15960, an intermediate plasmid used for constructing plasmids containing DNA sequences encoding G-CSF Ser17 with a new N-terminus and C-terminus. Plasmid pACYC177 (Chang, A. C. Y. and Cohen, S. N. J. Bacteriol. 134:1141-1156, 1978) DNA was digested with restriction enzymes HindIII and BamHI, resulting in a 3092 base pair HindIII, BamHI fragment. Plasmid, pMON13037 (WO 95/21254), DNA was digested with BglII and FspI, resulting in a 616 base pair BglII, FspI fragment. A second sample of plasmid, pMON13037, DNA was digested with NcoI and HindIII, resulting in a 556 base pair NcoI, HindIII fragment. The synthetic DNA oligonucleotides 1GGGSfor (SEQ ID NO:76) and 1GGGSrev (SEQ ID NO:77) were annealed to each other, and then digested with AflIII and FspI, resulting in a 21 base pair AflIII, FspI fragment. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and analyzed by restriction analysis to confirm the correct insert.
EXAMPLE 46 Construction of pMON15981
Construction of pMON15981, a plasmid containing DNA sequences encoding a multi-functional hematopoietic receptor agonist. Plasmid, pMON15960, DNA was digested with restriction enzyme SmaI and used as template in a PCR reaction using synthetic DNA oligonucleotides 38 stop (SEQ ID NO:65) and 39 start (SEQ ID NO:64) as primers, resulting in the amplification of a DNA fragment of 576 base pairs. The amplified fragment was digested with restriction enzymes HindIII and NcoI, resulting in a HindIII, NcoI fragment of 558 base pairs. Plasmid, pMON13181, DNA was digested with HindIII and AflIII, resulting in a HindIII, AflIII fragment of 4068 base pairs. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm the correct insert. The plasmid, pMON15981, contains the DNA sequence of (SEQ ID NO:155) which encodes the following amino acid sequence:
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla              
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn              
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer              
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro              
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr              
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly              
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu              
SerHisLysSerProAsnMetAlaTyrLysLeuCysHisProGluGluLeuValLeuLeu              
GlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln              
LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln              
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVal              
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu              
GlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGly              
ValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHis              
LeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeu              
ProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAla              
AlaLeuGlnGluLysLeuCysAlaThr   (SEQ ID NO:195)
EXAMPLE 47 Construction of pMON15982
Construction of pMON15982, a plasmid containing DNA sequences encoding a multi-functional hematopoietic receptor agonist. Plasmid, pMON15960, DNA was digested with restriction enzyme SmaI and used as template in a PCR reaction using synthetic DNA oligonucleotides 96 stop (SEQ ID NO:67) and 97 start (SEQ ID NO:66) as primers, resulting in the amplification of a DNA fragment of 576 base pairs. The amplified fragment was digested with restriction enzymes HindIII and NcoI, resulting in a HindIII, NcoI fragment of 558 base pairs. Plasmid, pMON13181, DNA was digested with HindIII and AflIII, resulting in a HindIII, AflIII fragment of 4068 base pairs. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm the correct insert. The plasmid, pMON15982, contains the DNA sequence of (SEQ ID NO:157) which encodes the following amino acid sequence:
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla              
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn              
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer              
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro              
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr              
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly              
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu              
SerHisLysSerProAsnMetAlaProGluLeuGlyProThrLeuAspThrLeuGlnLeu              
AspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaPro              
AlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAla              
GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeu              
ArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSer              
SerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAsp              
GlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeu              
ValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGln              
AlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGly              
LeuLeuGlnAlaLeuGluGlyIleSer   (SEQ ID NO:196)
EXAMPLE 48 Construction of pMON15965
Construction of pMON15965, a plasmid containing DNA sequences encoding a multi-functional hematopoietic receptor agonist. Plasmid, pMON15960, DNA was digested with restriction enzyme SmaI and used as template in a PCR reaction using synthetic DNA oligonucleotides 142 stop (SEQ ID NO:73) and 141 start (SEQ ID NO:72) as primers, resulting in the amplification of a DNA fragment of 576 base pairs. The amplified fragment was digested with restriction enzymes HindIII and NcoI, resulting in a HindIII, NcoI fragment of 558 base pairs. Plasmid, pMON13181, DNA was digested with HindIII and AflIII, resulting in a HindIII, AflIII fragment of 4068 base pairs. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm the correct insert. The plasmid, pMON15965, contains the DNA sequence of (SEQ ID NO:157) which encodes the following amino acid sequence:
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla              
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn              
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer              
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro              
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr              
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly              
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu              
SerHisLysSerProAsnMetAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuVal              
AlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGln              
ProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSer              
PheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGln              
GluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHis              
SerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGluAlaLeuGlnLeuAla              
GlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeu              
GluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAsp              
PheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro              
ThrGlnGlyAlaMetProAlaPheAla (SEQ ID NO:196)
EXAMPLE 49 Construction of pMON15966
Construction of pMON15966, a plasmid containing DNA sequences encoding a multi-functional hematopoietic receptor agonist. Plasmid, pMON15960, DNA was digested with restriction enzyme SmaI and used as template in a PCR reaction using synthetic DNA oligonucleotides 126 stop (SEQ ID NO:68) and 125 start (SEQ ID NO:69) as primers, resulting in the amplification of a DNA fragment of 576 base pairs. The amplified fragment was digested with restriction enzymes HindIII and NcoI, resulting in a HindIII, NcoI fragment of 558 base pairs. Plasmid, pMON13181, DNA was digested with HindIII and AflIII, resulting in a HindIII, AflIII fragment of 4068 base pairs. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm the correct insert. The plasmid, pMON15966, contains the DNA sequence of (SEQ ID NO:158) which encodes the following amino acid sequence:
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla              
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn              
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer              
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro              
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr              
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly              
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu              
SerHisLysSerProAsnMetAlaMetAlaProAlaLeuGlnProThrGlnGlyAlaMet              
ProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeu              
GlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGly              
SerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLys              
SerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCys              
AlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIle              
ProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSer              
GlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer              
ProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThr              
IleTrpGlnGlnMetGluGluLeuGly (SEQ ID NO:197)
EXAMPLE 50 Construction of pMON15967
Construction of pMON15967, a plasmid containing DNA sequences encoding a multi-functional hematopoietic receptor agonist. Plasmid, pMON15960, DNA was digested with restriction enzyme SmaI and used as template in a PCR reaction using synthetic DNA oligonucleotides 132 stop (SEQ ID NO:71) and 133 start (SEQ ID NO:70) as primers, resulting in the amplification of a DNA fragment of 576 base pairs. The amplified fragment was digested with restriction enzymes HindIII and NcoI, resulting in a HindIII, NcoI fragment of 558 base pairs. Plasmid, pMON13181, DNA was digested with HindIII and AflIII, resulting in a HindIII, AflIII fragment of 4068 base pairs. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm the correct insert. The plasmid, pMON15967, contains the DNA sequence of (SEQ ID NO: 159) which encodes the following amino acid sequence:
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla              
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn              
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer              
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro              
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr              
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly              
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu              
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe              
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer              
TyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeu              
GlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLys              
IleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHis              
ProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSer              
CysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPhe              
LeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeu              
AspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGlu              
LeuGlyMetAlaProAlaLeuGlnPro SEQ ID NO:198
EXAMPLE 51
Construction of pMON13180, an intermediate plasmid used for constructing Dlasmids that contain DNA sequence encoding multi-functional hematopoietic receptor agonists.
Plasmid, pMON13046 (WO 95/21254), DNA was digested with restriction endonucleases XmaI and SnaBI, resulting in a 4018 base pair vector fragment. The 4018 base pair XmaI-SnaBI fragment was purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.) in which the 25 base pair XmaI-SnaBI insert fragment is not retained. The complimentary pair of synthetic oligonucleotides, glyxal (SEQ ID NO:74) and glyxa2 (SEQ ID NO:75), were designed to remove sequence encoding a factor Xa cleavage site. When properly assembled these oligonucleotides also result in XmaI and SnaBI ends. The primers, Glyxa1 and glyxa2, were annealed in annealing buffer (20 mM Tris-HCl pH7.5, 10 mM MgCl2, 50 mM NaCl) by heating at 70° C. for ten minutes and allowed to slow cool. The 4018 base pair XmaI-SnaBI fragment from pMON13046 was ligated with the assembled oligonucleotides using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated from the transformants and analyzed using a PCR based assay. Plasmid DNA from selected transformants was sequenced to confirm the correct insertion of the oligonucleotides. The resulting plasmid was designated pMON13180 and contains the DNA sequence of (SEQ ID NO:258).
EXAMPLE 52
Construction of pMON13181. an intermediate plasmid used for constructing plasmids that contain DNA sequences encoding multi-functional hematopoietic receptor agonists.
Plasmid, pMON13047 (WO 95/21254), DNA was digested with restriction endonucleases XmaI and SnaBI, resulting in a 4063 base pair vector fragment. The 4063 base pair XmaI-SnaBI fragment was purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.) in which the 25 base pair XmaI-SnaBI insert fragment is not retained. The complimentary pair of synthetic oligonucleotides, glyxal (SEQ ID NO:74) and glyxa2 (SEQ ID NO:75), were designed to remove sequence encoding the factor Xa cleavage site. When properly assembled these oligonucleotides also result in XmaI and SnaBI ends. Glyxal and glyxa2 were annealed in annealing buffer by heating at 70° C. for ten minutes and allowed to slow cool. The 4063 base pair XmaI-SnaBI fragment from pMON13047 was ligated with the assembled oligonucleotides using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated from the transformants and analyzed using a PCR based assay. Plasmid DNA from selected transformants was sequenced to confirm the correct insertion of the oligonucleotides. The resulting plasmid was designated pMON13181 and contains the DNA sequence of (SEQ ID NO:257).
EXAMPLE 53 Construction of pMON13182
The new N-terminus/C-terminus gene in pMON13182 was created using Method I as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 39 start (SEQ ID NO:64) and L-11 start (SEQ ID NO:60). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 38 stop (SEQ ID NO:65) and L-11 stop (SEQ ID NO:61). The full-length new N terminus/C-terminus G-CSF Ser17 gene was created and amplified from the annealed Fragments Start and Stop using primers 39 start and 38 stop.
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The intermediate plasmid, pMON13180, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13182.
E. coli strain JM101 was transformed with pMON13182 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13182, contains the DNA sequence of (SEQ ID NO:94) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Tyr Lys Leu Cys               
His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro               
Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala               
Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly               
Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr               
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile               
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly               
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val               
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys               
Ala Thr (SEQ ID NO:166)
EXAMPLE 54 Construction of pMON13183
The new N-terminus/C-terminus gene in pMON13183 was created using Method I as described in Materials and Methods. "Fragment Start" was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 39 start (SEQ ID NO:64) and L-11 start (SEQ ID NO:60). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 38 stop (SEQ ID NO:65) and L-l1 stop (SEQ ID NO:61). The full-length new N terminus/C-terminus G-CSF Ser17 gene was created and amplified from the annealed Fragments Start and Stop using 39 start and 38 stop.
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The intermediate plasmid, pMON13181, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13183.
E. coli strain JM101 was transformed with pMON13183 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13183, contains the DNA sequence of (SEQ ID NO:95) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Tyr Lys Leu Cys               
His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro               
Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala               
Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly               
Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr               
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile               
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly               
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val               
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys               
Ala Thr  (SEQ ID NO:167)
EXAMPLE 55 Construction of pMON13184
The new N-terminus/C-terminus gene in pMON13184 was created using Method I as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 97 start (SEQ ID NO:66) and L-11 start (SEQ ID NO:60). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 96 stop (SEQ ID NO:67) and L-11 stop (SEQ ID NO:61). The full-length new N terminus/C-terminus G-CSF Ser17 gene was created and amplified from the annealed Fragments Start and Stop using 97 start and 96 stop.
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The intermediate plasmid, pMON13180, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13184.
E. coli strain JM101 was transformed with pMON13184 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13184, contains the DNA sequence of (SEQ ID NO:96) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Pro Glu Leu Gly               
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr               
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu               
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser               
Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu               
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys               
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu               
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys               
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His               
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly               
Ile Ser (SEQ ID NO:168)
EXAMPLE 56 Construction of pMON13185
The new N-terminus/C-terminus gene in pMON13185 was created using Method I as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 97 start (SEQ ID NO:66) and L-11 start (SEQ ID NO:60). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 96 stop (SEQ ID NO:67 and L-11 stop (SEQ ID NO:61). The full-length new N terminus/C-terminus G-CSF Ser17 gene was created and amplified from the annealed Fragments Start and Stop using 97 start and 96 stop.
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The intermediate plasmid, pMON13181, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13185.
E. coli strain JM101 was transformed with pMON13185 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13185, contains the DNA sequence of (SEQ ID NO:67) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Pne Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Pro Glu Leu Gly               
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr               
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu               
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser               
Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu               
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys               
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu               
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys               
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His               
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly               
Ile Ser (SEQ ID NO:169)
EXAMPLE 57 Construction of pMON13186
The new N-terminus/C-terminus gene in pMON13186 was created using Method I as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 126 start (SEQ ID NO:68) and L-11 start (SEQ ID NO:60). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 125 stop (SEQ ID NO:69) and L-11 stop (SEQ ID NO:61). The full-length new N terminus/C-terminus G-CSF Ser17 gene was created and amplified from the annealed Fragments Start and Stop using 126 start and 125 stop.
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The intermediate plasmid, pMON13180, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13186.
E. coli strain JM101 was transformed with pMON13186 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13186, contains the DNA sequence of (SEQ ID NO:98) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Met Ala Pro Ala               
Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe               
Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser               
Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro               
Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu               
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu               
Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val               
Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser               
Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu               
His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu               
Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu               
Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu               
Leu Gly (SEQ ID NO:170)
EXAMPLE 58 Construction of pMON13187
The new N-terminus/C-terminus gene in pMON13187 was created using Method I as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 126 start (SEQ ID NO:68) and L-11 start (SEQ ID NO:60). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 125 stop (SEQ ID NO:69) and L-11 stop (SEQ ID NO:61). The full-length new N terminus/C-terminus G-CSF Ser17 gene was created and amplified from the annealed Fragments Start and Stop using 126 start and 125 stop.
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The intermediate plasmid, pMON13181, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13187.
E. coli strain JM101 was transformed with pMON13187 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13187, contains the DNA sequence of (SEQ ID NO:99) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Met Ala Pro Ala               
Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe               
Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser               
Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro               
Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu               
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu               
Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val               
Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser               
Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu               
His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu               
Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu               
Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu               
Leu Gly  (SEQ ID NO:171)
EXAMPLE 59 Construction of pMON13188
The new N-terminus/C-terminus gene in pMON13188 was created using Method I as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 133 start (SEQ ID NO:70) and L-11 start (SEQ ID NO:60). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 132 stop (SEQ ID NO:71) and L-11 stop (SEQ ID NO:61). The full-length new N terminus/C-terminus G-CSF Ser17 gene was created and amplified from the annealed Fragments Start and Stop using 133 start and 132 stop.
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The intermediate plasmid, pMON13180, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13188.
E. coli strain JM101 was transformed with pMON13188 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13188, contains the DNA sequence of (SEQ ID NO:100) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Thr Gln Gly Ala               
Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val               
Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg               
Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser               
Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln               
Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys               
Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly               
Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln               
Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr               
Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly               
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr               
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu               
Gln Pro (SEQ ID NO:172)
EXAMPLE 60 Construction of pMON13189
The new N-terminus/C-terminus gene in pMON13189 was created using Method I as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 133 start (SEQ ID NO:70) and L-11 start (SEQ ID NO:60). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 132 stop (SEQ ID NO:71) and L-11 stop (SEQ ID NO:61). The full-length new N terminus/C-terminus G-CSF Ser17 gene was created and amplified from the annealed Fragments Start and Stop using 133 start and 132 stop.
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The intermediate plasmid, pMON13181, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13189.
E. coli strain JM101 was transformed with pMON13189 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13189, contains the DNA sequence of (SEQ ID NO:101) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala               
Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val               
Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg               
Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser               
Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln               
Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys               
Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly               
Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln               
Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr               
Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly               
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr               
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu               
Gln Pro   (SEQ ID NO:173)
EXAMPLE 61 Construction of pMON13190
The new N-terminus/C-terminus gene in pMON13190 was created using Method I as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 142 start (SEQ ID NO:72) and L-11 start (SEQ ID NO:60). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 141 stop (SEQ ID NO:73) and L-11 stop (SEQ ID NO:61). The full-length new N terminus/C-terminus G-CSF Ser17 gene was created and amplified from the annealed Fragments Start and Stop using 142 start and 141 stop.
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The intermediate plasmid, pMON13180, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13190.
E. coli strain JM101 was transformed with pMON13190 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13190, contains the DNA sequence of (SEQ ID NO:102) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser               
Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu               
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys               
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu               
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys               
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His               
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly               
Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp               
Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu               
Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala               
Phe Ala (SEQ ID NO:174)
EXAMPLE 62 Construction of pMON13191
The new N-terminus/C-terminus gene in pMON13191 was created using Method I as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 142 start (SEQ ID NO:72) and L-11 start (SEQ ID NO:60). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 141 stop (SEQ ID NO:73) and L-11 stop (SEQ ID NO:61). The full-length new N terminus/C-terminus G-CSF Ser17 gene was created and amplified from the annealed Fragments Start and Stop using 142 start and 141 stop.
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and HindIII and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The intermediate plasmid, pMON13181, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13191.
E. coli strain JM101 was transformed with pMON13191 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13191, contains the DNA sequence of (SEQ ID NO:103) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser               
Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu               
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys               
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu               
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys               
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His               
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly               
Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp               
Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu               
Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala               
Phe Ala (SEQ ID NO:175)
EXAMPLE 63 Construction of pMON13192
The new N-terminus/C-terminus gene in pMON13192 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF sequence in pMON13037 using the primer set, 39 start (SEQ ID NO:64) and P-bl start (SEQ ID NO:62). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 38 stop (SEQ ID NO:65) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease NcoI, and Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser17 gene and was digested with restriction endonucleases NcoI and HindIII. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser17 gene was isolated using Geneclean (Bio101, Vista, Calif.). The intermediate plasmid, pMON13180, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13192.
E. coli strain JM101 was transformed with pMON13192 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13192, contains the DNA sequence of (SEQ ID NO:104) which encodes the following amino acid sequence:
13192.Pept
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Tyr Lys Leu Cys               
His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro               
Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala               
Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly               
Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr               
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile               
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu               
Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu               
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu               
Lys Leu Cys Ala Thr (SEQ ID NO:176)
EXAMPLE 64 Construction of pMON13193
The new N-terminus/C-terminus gene in pMON13193 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 39 start (SEQ ID NO:64) and P-bl start (SEQ ID NO:62). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 38 stop (SEQ ID NO:65) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease NcoI, and Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser17 gene and was digested with restriction endonucleases NcoI and HindIII. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser17 gene was isolated using Geneclean (Bio101, Vista, Calif.). The intermediate plasmid, pMON13181, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13193.
E. coli strain JM101 was transformed with pMON13193 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13193, contains the DNA sequence of (SEQ ID NO:105) encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Tyr Lys Leu Cys               
His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro               
Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala               
Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly               
Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr               
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile               
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu               
Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu               
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu               
Lys Leu Cys Ala Thr (SEQ ID NO:177)
EXAMPLE 65 Construction of pMON25190
The new N-terminus/C-terminus gene in pMON25190 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF sequence in pMON13037 using the primer set, 97 start (SEQ ID NO:66) and P-bl start (SEQ ID NO:62). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 96 stop (SEQ ID NO:67) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease NcoI, and Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser17 gene and was digested with restriction endonucleases NcoI and HindIII. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser17 gene was isolated using Geneclean (Bio101, Vista, Calif.). The intermediate plasmid, pMON13180, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON25190.
E. coli strain JM101 was transformed with pMON25190 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON25190, contains the DNA sequence of (SEQ ID NO:106) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Pro Glu Leu Gly               
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr               
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu               
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr               
Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys               
Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu               
Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu               
Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu               
Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser               
Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala               
Leu Glu Gly Ile Ser  (SEQ ID NO:178)
EXAMPLE 66 Construction of pMON25191
The new N-terminus/C-terminus gene in pMON25191 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 97 start (SEQ ID NO:66) and P-bl start (SEQ ID NO:62). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 96 stop (SEQ ID NO:98) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease NcoI, and Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser17 gene and was digested with restriction endonucleases NcoI and HindIII. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser17 gene was isolated using Geneclean (Bio101, Vista, Calif.). The intermediate plasmid, pMON13181, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON25191.
E. coli strain JM101 was transformed with pMON25191 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON25191, contains the DNA sequence of (SEQ ID NO:107) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Pro Glu Leu Gly               
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr               
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu               
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr               
Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys               
Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu               
Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu               
Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu               
Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser               
Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala               
Leu Glu Gly Ile Ser (SEQ ID NO:179)
EXAMPLE 67 Construction of pMON13194
The new N-terminus/C-terminus gene in pMON13194 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 126 start (SEQ ID NO:68) and P-bl start (SEQ ID NO:62). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 125 stop (SEQ ID NO:67) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease NcoI, and Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser17 gene and was digested with restriction endonucleases NcoI and HindIII. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser17 gene was isolated using Geneclean (Bio101, Vista, Calif.). The intermediate plasmid, pMON13180, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13194.
E. coli strain JM101 was transformed with pMON13194 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13194, contains the DNA sequence of (SEQ ID NO:108) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Met Ala Pro Ala               
Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe               
Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser               
Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro               
Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu               
Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala               
Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu               
Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro               
Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu               
Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln               
Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr               
Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln               
Met Glu Glu Leu Gly (SEQ ID NO:180)
EXAMPLE 68 Construction of pMON13195
The new N-terminus/C-terminus gene in pMON13195 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 126 start (SEQ ID NO:68) and P-bl start (SEQ ID NO:62). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 125 stop (SEQ ID NO:69) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease NcoI, and Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser17 gene and was digested with restriction endonucleases NcoI and HindIII. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser17 gene was isolated using Geneclean (Bio101, Vista, Calif.). The intermediate plasmid, pMON13181, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13195.
E. coli strain JM101 was transformed with pMON13195 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13195, contains the DNA sequence of (SEQ ID NO:109) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Met Ala Pro Ala               
Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe               
Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser               
Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro               
Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu               
Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala               
Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu               
Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro               
Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu               
Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln               
Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr               
Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln               
Met Glu Glu Leu Gly (SEQ ID NO:181)
EXAMPLE 69 Construction of pMON13196
The new N-terminus/C-terminus gene in pMON13196 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF sequence in pMON13037 using the primer set, 133 start (SEQ ID NO:70) and P-bl start (SEQ ID NO:62). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 132 stop (SEQ ID NO:71) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease NcoI, and Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser17 gene and was digested with restriction endonucleases NcoI and HindIII. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser17 gene was isolated using Geneclean (Bio101, Vista, Calif.). The intermediate plasmid, pMON13180, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13196.
E. coli strain JM101 was transformed with pMON13196 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13196, contains the DNA sequence of (SEQ ID NO:110) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Thr Gln Gly Ala               
Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val               
Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg               
Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu Gly Pro Ala Ser               
Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg               
Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala               
Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His               
Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln               
Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu               
Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro               
Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp               
Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala               
Pro Ala Leu Gln Pro (SEQ ID NO:182)
EXAMPLE 70 Construction of pMON13197
The new N-terminus/C-terminus gene in pMON13197 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 133 start (SEQ ID NO:70) and P-bl start (SEQ ID NO:62). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 132 stop (SEQ ID NO:71) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease NcoI, and Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser17 gene and was digested with restriction endonucleases NcoI and HindIII. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser17 gene was isolated using Geneclean (Bio101, Vista, Calif.). The intermediate plasmid, pMON13181, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13197.
E. coli strain JM101 was transformed with pMON13197 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13197, contains the DNA sequence of (SEQ ID NO:lll) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Tyr Lys Leu Cys               
His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro               
Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala               
Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly               
Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr               
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile               
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu               
Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu               
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu               
Lys Leu Cys Ala Thr (SEQ ID NO:183)
EXAMPLE 71 Construction of pMON13198
The new N-terminus/C-terminus gene in pMON13198 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF sequence in pMON13037 using the primer set, 142 start (SEQ ID NO:72) and P-bl start (SEQ ID NO:62). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 141 stop (SEQ ID NO:73) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease NcoI, and Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser17 gene and was digested with restriction endonucleases NcoI and HindIII. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser17 gene was isolated using Geneclean (Bio101, Vista, Calif.). The intermediate plasmid, pMON13180, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13198.
E. coli strain JM101 was transformed with pMON13198 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13198, contains the DNA sequence of (SEQ ID NO:112) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr               
Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys               
Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu               
Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu               
Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu               
Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser               
Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala               
Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu               
Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met               
Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala               
Met Pro Ala Phe Ala (SEQ ID NO:184)
EXAMPLE 72 Construction of pMON13199
The new N-terminus/C-terminus gene in pMON13199 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 142 start (SEQ ID NO:72) and P-bl start (SEQ ID NO:62). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 141 stop (SEQ ID NO:73) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease NcoI, and Fragment Stop was digested with restriction endonuclease HindIII. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair NcoI-HindIII vector fragment of pMON3934.
The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser17 gene and was digested with restriction endonucleases NcoI and HindIII. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser17 gene was isolated using Geneclean (Bio101, Vista, Calif.). The intermediate plasmid, pMON13181, was digested with restriction endonucleases HindIII and AflIII, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, Wis.). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13199.
E. coli strain JM101 was transformed with pMON13199 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON13199, contains the DNA sequence of (SEQ ID NO:113) which encodes the following amino acid sequence:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile               
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr               
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp               
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu               
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro               
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro               
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Ser Ala Phe Gln               
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe               
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr               
Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys               
Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu               
Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu               
Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu               
Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser               
Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala               
Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu               
Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met               
Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala               
Met Pro Ala Phe Ala (SEQ ID NO:185)
EXAMPLE 73 Construction of Tandemly-Duplicated Plasmid Template, Syntan1
To create the tandemly-duplicated hIL-3 receptor agonist pMON13416 template, Syntan1, three DNAs were joined by means of ligation using T4 DNA ligase (Boehringer Mannheim). The three DNAs are: 1) pMON13046, containing hIL-3 receptor agonist pMON13416, digested with BstEII and SnaBI; 2) the annealed complimentary pair of synthetic oligonucleotides, L1syn.for (SEQ ID NO:48) and L1syn.rev (SEQ ID NO:49), which contain sequence encoding the linker that connects the C-terminal and N-terminal ends of the original protein and a small amount of surrounding pMON13416 sequence and which when properly assembled result in BstEII and ClaI ends; and 3) a portion of hIL-3 receptor agonist pMON13416 digested from pMON13046 with ClaT (DNA had been grown in the dam- cells, DM1 (Life Technologies)) and SnaBI. The digested DNAs were resolved on a 0.9% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101).
A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Miniprep DNA was isolated from the transformants, and the transformants were screened using a PCR based assay. Plasmid DNA from selected transformants was sequenced to obtain the correct template. The resulting plasmid was designated syntan1 and contains the DNA sequence of (SEQ ID NO:84).
EXAMPLE 74 Construction of Tandemly-Duplicated Template, Syntan3
To create the tandemly-duplicated hIL-3 receptor agonist pMON13416 template, syntan3, three DNAs were joined by means of ligation using T4 DNA ligase (Boehringer Mannheim). The three DNAs are: 1) pMON13046, containing hIL-3 receptor agonist pMON13416, digested with BstEII and SnaBI; 2) the annealed complimentary pair of synthetic oligonucleotides, L3syn.for (SEQ ID NO:50) and L3syn.rev (SEQ ID NO:51), which contain sequence encoding the linker that connects the C-terminal and N-terminal ends of the original protein and a small amount of surrounding pMON13416 sequence and which when properly assembled result in BstEII and SnaBI ends; and 3) a portion of hIL-3 receptor agonist pMON13416 digested from pMON13046 with ClaI (DNA had been grown in the dam- cells, DM1 (Life Technologies)) and SnaBI. The digested DNAs were resolved on a 0.9% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101).
A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Miniprep DNA was isolated from the transformants, and the transformants were screened using a PCR based assay. Plasmid DNA from selected transformants was sequenced to obtain the correct template. The resulting plasmid was designated syntan3 and contains the DNA sequence of (SEQ ID NO:85).
EXAMPLE 75 Construction of pMON31104
The new N-terminus/C-terminus gene in pMON31104 was created using Method III as described in Materials and Methods. The full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan1, using the primer set 35 start (SEQ ID NO:52) and 34 rev (SEQ ID NO:53).
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI. The digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.). The purified digested DNA fragment was ligated into the expression vector,pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). The pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31104.
E. coli strain JM101 was transformed with pMON31104 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON31104, contains the DNA sequence of (SEQ ID NO:86) which encodes the following amino acid sequence:
Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met               
Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala               
Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg               
Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg               
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu               
Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln               
Gln Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp Glu Ile Ile               
His His Leu Lys Arg Pro Pro Ala Pro Leu Tyr Val Glu Gly Gly               
Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn               
Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly               
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val               
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys               
Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly               
His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser               
Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly               
Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser               
Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala               
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met               
Ala Pro Ala Leu Gln Pro (SEQ ID NO:186)
EXAMPLE 76 Construction of pMON31105
The new N-terminus/C-terminus gene in pMON31105 was created using Method III as described in Materials and Methods. The full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan1, using the primer set 70 start (SEQ ID NO:54) and 69 rev (SEQ ID NO:55).
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI. The digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.). The purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). The pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31105.
E. coli strain JM101 was transformed with pMON31105 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON31105, contains the DNA sequence of (SEQ ID NO:87) which encodes the protein with the following amino acid sequence:
Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys               
Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile               
Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr               
Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser               
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg               
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp               
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu               
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Tyr Val Glu Gly Gly               
Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn               
Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly               
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val               
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys               
Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly               
His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser               
Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly               
Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser               
Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala               
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met               
Ala Pro Ala Leu Gln Pro (SEQ ID NO:187)
EXAMPLE 77 Construction of pMON31106
The new N-terminus/C-terminus gene in pMON31106 was created using Method III as described in Materials and Methods. The full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan1, using the primer set 91 start (SEQ ID NO:56) and 90 rev (SEQ ID NO:57).
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI. The digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.). The purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). The pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31106.
E. coli strain JM101 was transformed with pMON31106 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON31106, contains the DNA sequence of (SEQ ID NO:80) which encodes the protein with the following amino acid sequence:
Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln               
Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln               
Ala Gln Glu Gln Gln Gly Gly Gly Ser Asn Cys Ser Ile Met Ile               
Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu               
Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp               
Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val               
Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn               
Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Tyr Val Glu Gly Gly               
Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn               
Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly               
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val               
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys               
Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly               
His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser               
Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly               
Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser               
Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala               
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met               
Ala Pro Ala Leu Gln Pro  (SEQ ID NO:188)
EXAMPLE 78 Construction of pMON31107
The new N-terminus/C-terminus gene in pMON31107 was created using Method III as described in Materials and Methods. The full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan1, using the primer set 101 start (SEQ ID NO:58) and 100 rev (SEQ ID NO:59).
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI. The digested The DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.). The purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). The pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31107.
E. coli strain JM101 was transformed with pMON31107 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON31107, contains the DNA sequence of (SEQ ID NO:89) which encodes the following amino acid sequence:
Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu               
Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser Asn               
Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro               
Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val               
Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser               
Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu               
Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala               
Ala Pro Ser Arg His Pro Ile Ile Ile Lys Tyr Val Glu Gly Gly               
Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn               
Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala               
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg               
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu               
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly               
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val               
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys               
Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly               
His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser               
Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly               
Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser               
Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala               
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met               
Ala Pro Ala Leu Gln Pro (SEQ ID NO:189)
EXAMPLE 79 Construction of pMON31108
The new N-terminus/C-terminus gene in pMON31108 was created using Method III as described in Materials and Methods. The full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan3, using the primer set 35 start (SEQ ID NO:52) and 34 rev (SEQ ID NO:53).
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI. The digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.). The purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). The pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31108.
E. coli strain JM101 was transformed with pMON31108 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON31108, contains the DNA sequence of (SEQ ID NO:90) which encodes the following amino acid sequence:
Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met               
Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala               
Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg               
Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg               
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu               
Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln               
Gln Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Asn Cys               
Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro               
Ala Pro Leu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro               
Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu               
Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala               
Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala               
Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg               
His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe               
Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly               
Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His               
Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp               
Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly               
Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu               
Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu               
Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp               
Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro                   
(SEQ ID NO:190)
EXAMPLE 80 Construction of pMON31109
The new N-terminus/C-terminus gene in pMON31109 was created using Method III as described in Materials and Methods. The full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan3, using the primer set 70 start (SEQ ID NO:54) and 69 rev (SEQ ID NO:55).
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI. The digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.). The purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). The pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31109.
E. coli strain JM101 was transformed with pMON31109 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON31109, contains the DNA sequence of (SEQ ID NO:91) which encodes the following amino acid sequence:
Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys               
Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile               
Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr               
Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser               
Gly Gly Gly Ser Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp               
Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp               
Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp Arg               
Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys               
Asn Leu Glu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro               
Ser Gly Pro Ile Ser Phr Ile Asn Pro Ser Pro Pro Ser Lys Glu               
Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala               
Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala               
Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg               
His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe               
Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly               
Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His               
Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp               
Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly               
Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu               
Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu               
Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp               
Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro                   
(SEQ ID NO:191)
EXAMPLE 81 Construction of pMON31110
The new N-terminus/C-terminus gene in pMON31110 was created using Method III as described in Materials and Methods. The full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan3, using the primer set 91 start (SEQ ID NO:56) and 90 rev (SEQ ID NO:57).
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI. The digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.). The purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). The pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31110.
E. coli strain JM101 was transformed with pMON31110 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON31110, contains the DNA sequence of (SEQ ID NO:92) which encodes the following amino acid sequence:
Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln               
Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln               
Ala Gln Glu Gln Gln Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly               
Gly Ser Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu               
Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp               
Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn               
Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser               
Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser               
Ala Thr Ala Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro               
Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu               
Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala               
Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala               
Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg               
His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe               
Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly               
Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His               
Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp               
Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly               
Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu               
Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu               
Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp               
Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro                   
(SEQ ID NO:192)
EXAMPLE 82 Construction of pMON31111
The new N-terminus/C-terminus gene in pMON31111 was created using Method III as described in Materials and Methods. The full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan3, using the primer set 101 start (SEQ ID NO:58) and 100 rev (SEQ ID NO:59).
The resulting DNA fragment which contains the new gene was digested with restriction endonucleases NcoI and SnaBI. The digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (Bio101, Vista, Calif.). The purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.). The pMON13189 DNA had been previously digested with NcoI and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (Bio101, Vista, Calif.) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5α cells (Life Technologies, Gaithersburg, Md.). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31111.
E. coli strain JM101 was transformed with pMON31111 for protein expression and protein isolation from inclusion bodies.
The plasmid, pMON31111, contains the DNA sequence of (SEQ ID NO:93) which encodes the following amino acid sequence:
Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu               
Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser Gly               
Gly Gly Ser Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp Glu               
Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro               
Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn               
Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn               
Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln               
Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile               
Ile Ile Lys Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro               
Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu               
Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala               
Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala               
Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg               
His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe               
Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly               
Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His               
Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp               
Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly               
Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu               
Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu               
Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp               
Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro                   
(SEQ ID NO:193)
EXAMPLE 83 Construction of pMON31112
Construction of pMON31112, a plasmid containing DNA sequence encoding a multi-functional hematopoietic receptor agonist which activates the hIL-3 receptor and G-CSF receptor. Plasmid, pMON13189 DNA was digested with restriction enzymes NcoI and XmaI resulting in an NcoI, XmaI vector fragment that was isolated and purified from a 0.8% agarose gel. The DNA from a second plasmid, pMON13222 (WO 94/12639, U.S. Ser. No. 08/411,796) was digested with NcoI and EcoRI resulting in a 281 base pair NcoI, EcoRI fragment. This fragment was isolated and purified from a 1.0% agarose gel. Two oligonucleotides SYNNOXA1.REQ (SEQ ID NO:240) and SYNNOXA2.REQ (SEQ ID NO:241) were annealed and ligated with the 281 base pair DNA fragment from pMON13222 to the DNA vector fragment from pMON13189. A portion of the ligation mixture was then transformed into E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis to show the presence of an EcoRV fragment, and sequenced to confirm the correct inserts.
The plasmid, pMON31112, contains the DNA sequence of (SEQ ID NO:114) which encodes the following amino acid sequence:
MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProPro                 
LeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAsp                 
AsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGln                 
AsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAla                 
ThrAlaAlaProThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPhe                 
ArgArGlysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyr                 
ValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn                 
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAla                 
MetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSer                 
HisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro                 
SerGlyGlySerGlyGlySerGlnSerPheLeuLeuLysSerLeuGluGlnValArg                 
LysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeu                 
CysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaPro                 
LeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis                 
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGlu                 
LeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIle                 
TrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro                             
(SEQ ID NO:199)
Construction of pMON31113
Construction of pMON31113, a plasmid containing DNA sequence encoding a multi-functional hematopoietic receptor agonist which activates the hIL-3 receptor and G-CSF receptor. Plasmid, pMON13197 DNA was digested with restriction enzymes NcoI and XmaI resulting in an NcoI, XmaI vector fragment that was isolated and purified from a 0.8% agarose gel. The DNA from a second plasmid, pMON13239 (WO 94/12639, U.S. Ser. No. 08/411,796) was digested with NcoI and EcoRI resulting in a 281 base pair NcoI, EcoRI fragment. This fragment was isolated and purified from a 1.0% agarose gel. Two oligonucleotides SYNNOXA1.REQ (SEQ ID NO:240) and SYNNOXA2.REQ (SEQ ID NO:241) were annealed and ligated with the 281 base pair DNA fragment from pMON13239 to the DNA vector fragment from pMON13197. A portion of the ligation mixture was then transformed into E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis to show the presence of an EcoRV fragment, and sequenced to confirm the correct inserts.
The plasmid, pMON31113, contains the DNA sequence of (SEQ ID NO:115) which encodes the following amino acid sequence:
MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProPro                 
LeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGlu                 
AsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGln                 
AsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAla                 
ThrAlaAlaProThrArgHisProIleIleIleArgAspGlyAspTrpAsnGluPhe                 
ArgArgLysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyr                 
ValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn                 
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAla                 
MetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSer                 
HisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro                 
ThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGlu                 
GlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThr                 
TyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIlePro                 
TrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSer                 
GlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIle                 
SerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAla                 
ThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro                    
(SEQ ID NO:200)
EXAMPLE 85 Construction of pMON31114
Construction of pMON31114, a plasmid containing DNA sequence encoding a multi-functional hematopoietic receptor agonist which activates the hIL-3 receptor and G-CSF receptor. Plasmid, pMON13189 DNA was digested with restriction enzymes NcoI and XmaI resulting in an NcoI, XmaI vector fragment that was isolated and purified from a 0.8% agarose gel. The DNA from a second plasmid, pMON13239 (WO 94/12639, U.S. Ser. No. 08/411,796), was digested with NcoI and EcoRI resulting in a 281 base pair NcoI, EcoRI fragment. This fragment was isolated and purified from a 1.0% agarose gel. Two oligonucleotides SYNNOXA1.REQ (SEQ ID NO:240) and SYNNOXA2.REQ (SEQ ID NO:241) were annealed and ligated with the 281 base pair DNA fragment from pMON13239 to the DNA vector fragment from pMON13189. A portion of the ligation mixture was then transformed into E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis to show the presence of an EcoRV fragment, and sequenced to confirm the correct inserts.
The plasmid, pMON31114, contains the DNA sequence of (SEQ ID NO:116) which encodes the following amino acid sequence:
MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProPro                 
LeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspI1eLeuMetGlu                 
AsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGln                 
AsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProcysLeuProLeuAla                 
ThrAlaAlaProThrArgHisProIleIleIleArgAspGlyAspTrpAsnGluPhe                 
ArgArgLysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyr                 
ValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn                 
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAla                 
MetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSer                 
HisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro                 
SerGlyGlySerGlyGlySerGlnSerPheLeuLeuLysSerLeuGluGlnValArg                 
LysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeu                 
CysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaPro                 
LeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHis                 
SerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGlu                 
LeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIle                 
TrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro                             
(SEQ ID NO:201)
EXAMPLE 86 Construction of pMON31115
Construction of pMON31115, a plasmid containing DNA sequence encoding a multi-functional hematopoietic receptor agonist which activates the hIL-3 receptor and G-CSF receptor. Plasmid, pMON13197 DNA was digested with restriction enzymes NcoI and XmaI resulting in an NcoI, XmaI vector fragment that was isolated and purified from a 0.8% agarose gel. The DNA from a second plasmid, pMON13222, was digested with NcoI and EcoRI resulting in a 281 base pair NcoI, EcoRI fragment. This fragment was isolated and purified from a 1.0% agarose gel. Two oligonucleotides SYNNOXA1.REQ (SEQ ID NO:240) and SYNNOXA2.REQ (SEQ ID NO:241) were annealed and ligated with the 281 base pair DNA fragment from pMON13222 to the DNA vector fragment from pMON13197. A portion of the ligation mixture was then transformed into E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis to show the presence of an EcoRV fragment, and sequenced to confirm the correct inserts.
The plasmid, pMON31115, contains the DNA sequence of (SEQ ID NO:117) which encodes the following amino acid sequence:
MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProPro                 
LeuProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAsp                 
AsnAsnLeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGln                 
AsnAlaSerAlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAla                 
ThrAlaAlaProThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPhe                 
ArgArgLysLeuThrPheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyr                 
ValGluGlyGlyGlyGlySerProGlyGluProSerGlyProIleSerThrIleAsn                 
ProSerProProSerLysGluSerHisLysSerProAsnMetAlaThrGlnGlyAla                 
MetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSer                 
HisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnPro                 
ThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGlu                 
GlnValargLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThr                 
TyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIlePro                 
TrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSer                 
GlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIle                 
SerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAla                 
ThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro                    
(SEQ ID NO:202)
EXAMPLE 87
Determination of the in vitro activity of multi-functional hematopoietic receptor agonist proteins
The protein concentration of the multi-functional hematopoietic receptor agonist protein can be determined using a sandwich ELISA based on an affinity purified polyclonal antibody. Alternatively the protein concentration can be determined by amino acid composition analysis. The bioactivity of the multi-functional hematopoietic receptor agonist can be determined in a number of in vitro assays. For example a multi-functional hematopoietic receptor agonist which binds the hIL-3 receptor and G-CSF receptor can be assayed in cell proliferation assays using cell lines expressing the hIL-3 and/or G-CSF receptors. One such assay is the AML-193 cell proliferation assay. AML-193 cells respond to IL-3 and G-CSF which allows for the combined bioactivity of the IL-3/G-CSF multi-functional hematopoietic receptor agonist to be determined. Another such assay is the TF1 cell proliferation assay.
In addition other factor dependent cell lines, such as M-NFS-60 (ATCC. CRL 1838) or 32D which are murine IL-3 dependent cell line, may be used. The activity of IL-3 is species specific whereas G-CSF is not, therefore the bioactivity of the G-CSF component of the IL-3/G-CSF multi-functional hematopoietic receptor agonist can be determined independently. Cell lines, such as BHK or murine Baf/3, which do not express the receptor for a given ligand can be transfected with a plasmid containing a gene encoding the desired receptor. An example of such a cell line is BaF3 transfected with the hG-CSF receptor (BaF3/hG-CSF). The activity of the multi-functional hematopoietic receptor agonist in these cell lines can be compared with hIL-3 or G-CSF alone or together. The bioactivity of examples of multi-functional hematopoietic receptor agonists of the present invention assayed in the BaF3/hG-CSF cell proliferation and TF1 cell proliferation assays is shown in Table 5 and Table 6. The bioactivity of the multi-functional hematopoietic receptor agonist is expressed as relative activity compared with a standard protein pMON13056 (WO 95/21254). The bioactivity of examples of multi-functional hematopoietic receptor agonists of the present invention assayed in the BaF3/c-mpl cell proliferation and TF1 cell proliferation assays is shown in Table 7 and Table 8.
              TABLE 5                                                     
______________________________________                                    
CELL PROLIFERATIVE ACTIVITY                                               
OF DUAL IL-3/G-CSF RECEPTOR AGONISTS                                      
           BaF3/hG-CSF receptor                                           
                         TF1                                              
               cell proliferation                                         
                              cell proliferation                          
                                            assay                         
pMON       relative activity*                                             
                            relative activity*                            
______________________________________                                    
13182      0.015         1.1                                              
13183                    0.02                                             
                                              nd                          
13184                    0.01                                             
                                             0.3                          
13185                   0.023                                             
                                             0.36                         
13186                    0.36                                             
                                             0.45                         
13187                    0.07                                             
                                             0.26                         
13188                    0.64                                             
                                             1.3                          
13189                    0.58                                             
                                             1.37                         
13190                   0.045                                             
                                             1.2                          
13191                    0.14                                             
                                             2.7                          
13192                    0.09                                             
                                             2.2                          
13193                    0.06                                             
                                             3.0                          
25190                                          nd                         
25191                    0.43                                             
                                             1.2                          
13194                                          nd                         
13195                    1.3                                              
                                              4.3                         
13196                    0.66                                             
                                             0.5                          
13197                    0.6                                              
                                              0.77                        
13198                    0.6                                              
                                              0.5                         
13199                                          nd                         
15982                    0.7                                              
                                              1.9                         
15981                   0.068                                             
                                             1.2                          
15965                    0.7                                              
                                              0.82                        
15966                    0.36                                             
                                             1.48                         
15967                    0.62                                             
                                             1.37                         
______________________________________                                    
 nd = not determined                                                      
 *The bioactivity of the multifunctional hematopoietic receptor agonist is
 expressed as relative activity compared with a standard protein pMON13056
 n = 3 or greater                                                         

              TABLE 6                                                     
______________________________________                                    
CELL PROLIFERATIVE ACTIVITY                                               
OF DUAL IL-3/G-CSF RECEPTOR AGONISTS                                      
           BaF3/hG-CSF receptor                                           
                         TF1                                              
           cell proliferation                                             
                            cell proliferation                            
           assay                          assay                           
pMON                  relative activity                                   
                              relative activity                           
______________________________________                                    
31104      +             +                                                
31105                   +                                                 
                                               +                          
31106                   +                                                 
                                               +                          
31107                  nd                                                 
                                             nd                           
31108                   +                                                 
                                               +                          
31109                   +                                                 
                                               +                          
31110                  nd                                                 
                                             nd                           
31111                  nd                                                 
                                             nd                           
31112                   +                                                 
                                               +                          
31113                   +                                                 
                                               +                          
31114                   +                                                 
                                               +                          
31115                   +                                                 
                                               +                          
31116                  nd                                                 
                                             nd                           
31117                  nd                                                 
                                             nd                           
______________________________________                                    
 nd = not determined                                                      
 † The bioactivity (n = 1 or 2) of the multifunctional hematopoieti
 receptor agonist is expressed as relative activity compared with a       
 standard protein pMON13056.                                              
 "+" indicates that the molecule was comparable to pMON13056.             

              TABLE 7                                                     
______________________________________                                    
CELL PROLIFERATION ACTIVITY                                               
           Baf3/c-mpl receptor                                            
                         TF1                                              
                cell proliferation                                        
                             cell proliferation                           
           assay                            assay                         
pMON       activity*                     activity                         
______________________________________                                    
28505      -             +                                                
28506                    +                           -                    
28507                    +                           -                    
28508                    +                           -                    
28509                    +                           -                    
28510                    +                           -                    
28511                                             +                       
28512                                             +                       
28513                                             +                       
28514                                             +                       
28519                    +                           -                    
28520                    +                           -                    
28521                    +                           -                    
28522                    +                           -                    
28523                    +                           -                    
28524                    +                           -                    
28525                                             +                       
28526                                             +                       
28533                                              +                      
28534                    +                           -                    
28535                    +                           -                    
28536                    +                           -                    
28537                                          +                          
28538                    +                           -                    
28539                                             +                       
28540                                             +                       
28541                                             +                       
28542                                             +                       
28543                                             +                       
28544                                             +                       
28545                                             +                       
______________________________________                                    
 *Activity measured in the Baf3 cell line transfected with the cmpl       
 receptor, relative to cmpl ligand (1-153).                               
 † Activity measured relative to pMON13056.
In a similar manner other factor dependent cell lines known to those skilled in the art can be used to measure the bioactivity of the desired multi-functional hematopoietic receptor agonist. The methylcellulose assay can be used to determine the effect of the multi-functional hematopoietic receptor agonists on the expansion of the hematopoietic progenitor cells and the pattern of the different types of hematopoietic colonies in vitro. The methylcellulose assay can provide an estimate of precursor frequency since one measures the frequency of progenitors per 100,000 input cells. Long term, stromal dependent cultures have been used to delineate primitive hematopoietic progenitors and stem cells. This assay can be used to determine whether the multi-functional hematopoietic receptor agonist stimulates the expansion of very primitive progenitors and/or stem cells. In addition, limiting dilution cultures can be performed which will indicate the frequency of primitive progenitors stimulated by the multi-functional hematopoietic receptor agonist.
              TABLE 8                                                     
______________________________________                                    
                       c-mpl receptor agonist                             
          IL-3 agonist activity                                           
                       activity                                           
          (AML cell    (Baf/3-c-mpl cell                                  
pMON #    proliferation assay)                                            
                       proliferation assay                                
______________________________________                                    
28505     +            -                                                  
28506                   -      +                                          
28507                   -      +                                          
28508                   -      +                                          
28509                   -      +                                          
28510                   -      +                                          
28511                                         +                           
28512                                         +                           
28513                                         +                           
28514                                         +                           
28515                                         +                           
28519                   -      +                                          
28520                   -      +                                          
28521                   -      +                                          
28522                   -      +                                          
28523                   -      +                                          
28524                   -      +                                          
28525                                         +                           
28526                                         +                           
28527                                         +                           
28528                                         +                           
28529                                         +                           
28535                   -     +                                           
28539                                          +                          
28540                                          +                          
28541                                          +                          
28542                                          +                          
28545                                          +                          
______________________________________
EXAMPLE 88
G-CSF variants which contain single or multiple amino acid substitutions were made using PCR mutagenesis techniques as described in WO 94/12639 and WO 94/12638. These and other variants (i.e. amino acid substitutions, insertions or deletions and N-terminal or C-terminal extensions) could also be made, by one skilled in the art, using a variety of other methods including synthetic gene assembly or site-directed mutagenesis (see Taylor et al., Nucl. Acids Res., 13: 7864-8785 [1985]; Kunkel et al., Proc. Natl. Acad. Sci. USA, 82: 488-492 [1985]; Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., [1989], (WO 94/12639) and (WO 94/12638)). These substitutions can be made one at a time or in combination with other amino acid substitutions, and/or deletions, and/or insertions and/or extensions. After sequence verification of the changes, the plasmid DNA can be transfected into an appropriate mammalian cell, insect cell or bacterial strain such as E. coli for production. Known variants of G-CSF, which are active, include substitutions at positions 1 (Thr to Ser, Arg or Gly, 2 (Pro to Leu), 3 (Leu to Arg or Ser) and 17 (Cys to Ser) and deletions of amino acids 1-11 (Kuga et al. Biochemicla and Biophysical Research Comm. 159:103-111 (1989)). These G-CSF amino acid substitution variants can be used as the template to create the G-CSF receptor agonists in which a new N-terminus and new C-terminus are created. Examples of G-CSF amino acid substitution variants are shown in Table 9.
EXAMPLE 89
Bioactivity determination of G-CSF amino acid substitution variants
The G-CSF amino acid substitution variants can be assayed for cell proliferation activity using the Baf/3 cell line transfected with the human G-CSF receptor. The bioactivity of examples of G-CSF amino acid substitution variants is shown in Table 9 relative to native human G-CSF. A "+" indicates a comparable activity to native and a "-" indicates significantly reduced or no measurable activity.
              TABLE 9                                                     
______________________________________                                    
CELL PROLIFERATION ACTIVITY OF G-CSF VARIANTS IN BAF3                     
CELL LINE TRANSFECTED WITH THE HUMAN G-CSF RECEPTOR                       
aa position                                                               
         native aa     mutant aa                                          
                                activity*                                 
______________________________________                                    
13       Phe           Ser      +                                         
13                    Phe                                                 
                                              +                           
13                    Phe                                                 
                                              +                           
13                    Phe                                                 
                                              +                           
16                    Lys                                                 
                                              +                           
16                    Lys                                                 
                                              +                           
16                    Lys                                                 
                                              +                           
16                    Lys                                                 
                                              +                           
18                    Leu                                                 
                                              +                           
18                    Leu                                                 
                                              +                           
18                    Leu                                                 
                                              +                           
18                    Leu                                                 
                                              +                           
18                    Leu                                                 
                                              +                           
19                    Glu                                                 
                                -  Ala                                    
19                    Glu                                                 
                                -  Thr                                    
19                    Glu                                                 
                                -  Arg                                    
19                    Glu                                                 
                                -  Pro                                    
19                    Glu                                                 
                                -  Leu                                    
19                    Glu                                                 
                                -  Ser                                    
22                    Arg                                                 
                                              +                           
22                    Arg                                                 
                                              +                           
22                    Arg                                                 
                                              +                           
22                    Arg                                                 
                                              +                           
24                    Ile                                                 
                                              +                           
24                    Ile                                                 
                                              +                           
24                    Ile                                                 
                                              +                           
27                     Asp                                                
                                               +                          
30                     Ala                                                
                                               +                          
30                     Ala                                                
                                               +                          
34                     Lys                                                
                                               +                          
43                     His                                                
                                               +                          
43                     His                                                
                                               +                          
43                     His                                                
                                               +                          
43                     His                                                
                                               +                          
43                     His                                                
                                               +                          
43                     His                                                
                                               +                          
43                     His                                                
                                               +                          
43                     His                                                
                                               +                          
43                     His                                                
                                               +                          
44                     Pro                                                
                                               +                          
44                     Pro                                                
                                               +                          
44                     Pro                                                
                                               +                          
44                     Pro                                                
                                               +                          
44                     Pro                                                
                                               +                          
44                     Pro                                                
                                               +                          
44                     Pro                                                
                                               +                          
44                     Pro                                                
                                               +                          
44                     Pro                                                
                                               +                          
46                     Glu                                                
                                               +                          
46                     Glu                                                
                                               +                          
47                     Leu                                                
                                               +                          
49                     Leu                                                
                                               +                          
49                     Leu                                                
                                               +                          
49                     Leu                                                
                                               +                          
50                     Leu                                                
                                               +                          
54                     Leu                                                
                                               +                          
67                    Gln                                                 
                                               +                          
67                    Gln                                                 
                                               +                          
67                    Gln                                                 
                                               +                          
70                    Gln                                                 
                                               +                          
70                    Gln                                                 
                                               +                          
70                    Gln                                                 
                                               +                          
70                    Gln                                                 
                                               +                          
104                   Asp                                                 
                                               +                          
104                   Asp                                                 
                                               +                          
108                   Leu                                                 
                                               +                          
108                   Leu                                                 
                                               +                          
108                   Leu                                                 
                                               +                          
108                   Leu                                                 
                                               +                          
108                   Leu                                                 
                                               +                          
108                   Leu                                                 
                                               +                          
115                   Thr                                                 
                                               +                          
115                   Thr                                                 
                                               +                          
115                   Thr                                                 
                                               +                          
144                   Phe                                                 
                                               +                          
144                   Phe                                                 
                                               +                          
144                   Phe                                                 
                                               +                          
144                   Phe                                                 
                                               +                          
144                   Phe                                                 
                                               +                          
146                   Arg                                                 
                                               +                          
147                   Arg                                                 
                                               +                          
156                   His                                                 
                                -    Asp                                  
156                   His                                                 
                                               +                          
156                   His                                                 
                                               +                          
159                   Ser                                                 
                                               +                          
159                   Ser                                                 
                                               +                          
159                   Ser                                                 
                                               +                          
159                   Ser                                                 
                                               +                          
159                   Ser                                                 
                                               +                          
162                   Glu                                                 
                                -    Gly                                  
162                   Glu                                                 
                                               +                          
162                   Glu                                                 
                                               +                          
163                   Val                                                 
                                               +                          
163                   Val                                                 
                                               +                          
163                   Val                                                 
                                               +                          
165                   Tyr                                                 
                                              nd                          
169                   Ser                                                 
                                               +                          
169                   Ser                                                 
                                               +                          
169                   Ser                                                 
                                               +                          
170                   His                                                 
                                               +                          
170                   His                                                 
                                               +                          
______________________________________                                    
 *activity relative to native hGCSF                                       
 nd = not determined
EXAMPLE 90 Cysteine Substitution Variants
The multi-functional receptor agonists may comprise sequence rearranged c-mpl receptor agonist, which also have the substitution of the cysteine residues at position 7 and/or 151 with an another amino acid, which can be prepared by the methods described in Examples 1-89 and by other methods known to those skilled in the art. One such c-mpl receptor agonist has the breakpoint at 115/116 and alanine at positions 7 and 151. This c-mpl receptor agonist has the following amino acid:
MetAlaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis              
LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuAlaValArg              
GluPheGlyGlyAsnMetAlaSerProAlaProProAlaAlaAspLeuArgValLeuSer              
LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis              
ProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThr              
GlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGly              
ValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeu              
SerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuPro
ProGln (SEQ ID NO:284), and is encoded by the following DNA sequence;
  1                                                                       
   ATGGCTGGCA GGACCACAGC TCACAAGGAT CCCAATGCCA TCTTCCTGAG                 
 51                                                                       
     CTTCCAACAC CTGCTCCGAG GAAAGGTGCG TTTCCTGATG CTTGTAGGAG               
101                                                                       
     GGTCCACCCT CGCCGTCAGG GAATTCGGCG GCAACATGGC GTCTCCGGCG               
151                                                                       
     CCGCCTGCTG CTGACCTCCG AGTCCTCAGT AAACTGCTTC GTGACTCCCA               
201                                                                       
     TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AGAGGTTCAC CCTTTGCCTA               
251                                                                       
     CACCTGTCCT GCTGCCTGCT GTGGACTTTA GCTTGGGAGA ATGGAAAACC               
301                                                                       
     CAGATGGAGG AGACCAAGGC ACAGGACATT CTGGGAGCAG TGACCCTTCT               
351                                                                       
     GCTGGAGGGA GTGATGGCAG CACGGGGACA ACTGGGACCC ACTTGCCTCT               
401                                                                       
     CATCCCTCCT GGGGCAGCTT TCTGGACAGG TCCGTCTCCT CCTTGGGGCC               
451                                                                       
     CTGCAGAGCC TCCTTGGAAC CCAGCTTCCT CCACAG                              
              (SEQ ID NO:287).
Another c-mpl receptor agonist has the breakpoint at 81/82 and alanine at positions 7 and 151. This c-mpl receptor agonist has the following amino acid;
MetAlaGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeu              
LeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThr              
AlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysVal              
ArgPheLeuMetLeuValGlyGlySerThrLeuAlaValArgGluPheGlyGlyAsnMet              
AlaSerProAlaProProAlaAlaAspLeuArgValLeuSerLysLeuLeuArgAspSer              
HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVal              
LeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLys              
AlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGly
GlnLeu, (SEQ ID NO:285), and is encoded by the following DNA sequence;
  1                                                                       
   ATGGCTGGAC CCACTTGCCT CTCATCCCTC CTGGGGCAGC TTTCTGGACA                 
 51                                                                       
    GGTCCGTCTC CTCCTTGGGG CCCTGCAGAG CCTCCTTGGA ACCCAGCTTC                
101                                                                       
    CTCCACAGGG CAGGACCACA GCTCACAAGG ATCCCAATGC CATCTTCCTG                
151                                                                       
    AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG CGTTTCCTGA TGCTTGTAGG                
201                                                                       
    AGGGTCCACC CTCGCCGTCA GGGAATTCGG CGGCAACATG GCGTCTCCGG                
251                                                                       
    CGCCGCCTGC TGCTGACCTC CGAGTCCTCA GTAAACTGCT TCGTGACTCC                
301                                                                       
    CATGTCCTTC ACAGCAGACT GAGCCAGTGC CCAGAGGTTC ACCCTTTGCC                
351                                                                       
    TACACCTGTC CTGCTGCCTG CTGTGGACTT TAGCTTGGGA GAATGGAAAA                
401                                                                       
    CCCAGATGGA GGAGACCAAG GCACAGGACA TTCTGGGAGC AGTGACCCTT                
451                                                                       
    CTGCTGGAGG GAGTGATGGC AGCACGGGGA CAACTG                               
              (SEQ ID NO:286)
EXAMPLES 91-103
The plasmids in Table 10 contain genes encoding multi-functional hematopoietic receptor agonists comprising a sequence rearranged G-CSF receptor agonists that were made by the method of Horlich et al (Protein Eng. 5:427-431, 1992). As described in Materials and Methods, the tandem repeat of the G-CSF Ser17 gene was maintained on a pACYC177 based plasmid (Chang and Cohen, J. Bacteriol. 1341141-1156, 1978), containing the sequence; GAG ATG GCT, encoding; Asp Met Ala, following immediately downstream of amino acid 174 of the first copy of the G-CSF Ser17 gene and immediately preceeding amino acid 1 of the second copy of the G-CSF Ser17 gene. The resulting sequence rearranged G-CSF receptor agonists have the linker; Asp Met Ala, between the original C-terminus and original N-terminus of G-CSF Ser17. The sequence rearranged G-CSF receptor agonists encoded by the plasmids of Table 10 were identified using a G-CSF receptor binding screen (Wantanabe et al. Analyt. Biochem 195:38-44, 1991). The multi-functional receptor agonists shown in Table 10 had G-CSF receptor binding comparable to or better than native recombinant hG-CSF.
              TABLE 10                                                    
______________________________________                                    
plasmid                        protein                                    
designation                                                               
          breakpoint                                                      
                   gene sequence                                          
                                 sequence                                 
______________________________________                                    
pMON16017                                                                 
        2-3        SEQ ID NO:294                                          
                               SEQ ID NO:306                              
pMON16018                                                                 
            10-11       SEQ ID NO:288                                     
                                SEQ ID NO:300                             
pMON16019                                                                 
            12-13       SEQ ID NO:291                                     
                                SEQ ID NO:303                             
pMON16021                                                                 
            48-49       SEQ ID NO:295                                     
                                SEQ ID NO:307                             
pMON16022                                                                 
            59-60       SEQ ID NO:296                                     
                                SEQ ID NO:308                             
pMON16023                                                                 
            66-67       SEQ ID NO:297                                     
                                SEQ ID NO:309                             
pMON16024                                                                 
            68-69       SEQ ID NO:298                                     
                                SEQ ID NO:310                             
pMON16025                                                                 
            122-123                                                       
                      SEQ ID NO:289                                       
                                SEQ ID NO:301                             
pMON16028                                                                 
            158-159                                                       
                      SEQ ID NO:292                                       
                                SEQ ID NO:304                             
pMON16025                                                                 
            70-71       SEQ ID NO:299                                     
                                SEQ ID NO:311                             
pMON16027                                                                 
            124-125                                                       
                      SEQ ID NO:290                                       
                                SEQ ID NO:302                             
pMON16020                                                                 
            18-19       SEQ ID NO:293                                     
                                SEQ ID NO:305                             
pMON16029                                                                 
            169-170                                                       
                      SEQ ID NO:313                                       
                                SEQ ID NO:312                             
______________________________________
Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.
More details concerning the molecular biology techniques, protein purification and bioassays can be found in WO 94/12639, WO 94/12638, WO 95/20976, WO 95/21197, WO 95/20977, WO 95/21254, are hereby incorporated by reference in their entirety.
All references, patents or applications cited herein are incorporated by reference in their entirety as if written herein.
Various other examples will be apparent to the person skilled in the art after reading the present disclosure without departing from the spirit and scope of the invention. It is intended that all such other examples be included within the scope of the appended claims.
__________________________________________________________________________
#             SEQUENCE LISTING                                            
- (1) GENERAL INFORMATION:                                                
-    (iii) NUMBER OF SEQUENCES: 313                                       
- (2) INFORMATION FOR SEQ ID NO:1:                                        
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 174 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: protein                                         
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 1                                                 
#/note= "Xaa at position 1 is Thr,                                        
               Ser, Arg, - # Tyr or Gly;"                                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 2                                                 
#/note= "Xaa at position 2 is Pro or                                      
               Leu;"                                                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 3                                                 
#/note= "Xaa at position 3 is Leu,                                        
#or Ser;"      Arg, Tyr                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 13                                                
#/note= "Xaa at position 13 is Phe,                                       
               Ser, His, - # Thr or Pro;"                                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 16                                                
#/note= "Xaa at position 16 is Lys,                                       
               Pro, Ser, - # thr or His;"                                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 17                                                
#/note= "Xaa at position 17 is Cys,                                       
               Ser, Gly, - # Ala, Ile, Tyr or Arg;"                       
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 18                                                
#/note= "Xaa at position 18 is Leu,                                       
               Thr, Pro, - # His, Ile or Cys;"                            
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 22                                                
#/note= "Xaa at position 22 is Arg,                                       
               Tyr, Ser, - # Thr or Ala;"                                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 24                                                
#/note= "Xaa at position 24 is Ile,                                       
#or Leu;"      Pro, Tyr                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 27                                                
#/note= "Xaa at position 27 is Asp,                                       
               or Gly;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 30                                                
#/note= "Xaa at position 30 is Ala,                                       
#or Gly;"      Ile, Leu                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 34                                                
#/note= "Xaa at position 34 is Lys                                        
               or Ser;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 36                                                
#/note= "Xaa at position 36 is Cys                                        
               or Ser;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 42                                                
#/note= "Xaa at position 42 is Cys                                        
               or Ser;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 43                                                
#/note= "Xaa at position 43 is His,                                       
               Thr, Gly, - # Val, Lys, Trp, Ala, Arg, Cys, or Leu;"       
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 44                                                
#/note= "Xaa at position 44 is Pro,                                       
               Gly, Arg, - # Asp, Val, Ala, His, Trp, Gln, or Thr;"       
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 46                                                
#/note= "Xaa at position 46 is Glu,                                       
               Arg, Phe, - # Arg, Ile or Ala;"                            
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 47                                                
#/note= "Xaa at position 47 is Leu                                        
               or Thr;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 49                                                
#/note= "Xaa at position 49 is Leu,                                       
#or Ser;"      Phe, Arg                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 50                                                
#/note= "Xaa at position 50 is Leu,                                       
               Ile, His, - # Pro or Tyr;"                                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 54                                                
#/note= "Xaa at position 54 is Leu                                        
               or His;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 64                                                
#/note= "Xaa at position 64 is Cys                                        
               or Ser;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 67                                                
#/note= "Xaa at position 67 is Gln,                                       
#or Cys;"      Lys, Leu                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 70                                                
#/note= "Xaa at position 70 is Gln,                                       
               Pro, Leu, - # Arg or Ser;"                                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 74                                                
#/note= "Xaa at position 74 is Cys                                        
               or Ser;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 104                                               
#/note= "Xaa at position 104 is Asp,                                      
#Val;"         Gly or                                                     
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 108                                               
#/note= "Xaa at position 108 is Leu,                                      
               Ala, Val, - # Arg, Trp, Gln or Gly;"                       
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 115                                               
#/note= "Xaa at position 115 is Thr,                                      
#or Ala;"      His, Leu                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 120                                               
#/note= "Xaa at position 120 is Gln,                                      
               Gly, Arg, - # Lys or His"                                  
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 123                                               
#/note= "Xaa at position 123 is Glu,                                      
#or Thr"       Arg, Phe                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 144                                               
#/note= "Xaa at position 144 is Phe,                                      
               His, Arg, - # Pro, Leu, Gln or Glu;"                       
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 146                                               
#/note= "Xaa at position146 is Arg                                        
               or Gln;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 147                                               
#/note= "Xaa ap position 147 is Arg                                       
               or Gln;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 156                                               
#/note= "Xaa at position 156 is His,                                      
#Ser;"         Gly or                                                     
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 159                                               
#/note= "Xaa at position 159 is Ser,                                      
               Arg, Thr, - # Tyr, Val or Gly;"                            
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 162                                               
#/note= "Xaa at position 162 is Glu,                                      
#or Trp;"      Leu, Gly                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 163                                               
#/note= "Xaa at position 163 is Val,                                      
#or Ala;"      Gly, Arg                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 169                                               
#/note= "Xaa at position 169 is Arg,                                      
               Ser, Leu, - # Arg or Cys;"                                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 170                                               
#/note= "Xaa at position 170 is His,                                      
#Ser;"         Arg or                                                     
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:                             
- Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gl - #n Ser Xaa Leu Leu Xaa     
#                15                                                       
- Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xa - #a Gly Ala Xaa Leu Gln     
#            30                                                           
- Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xa - #a Xaa Glu Xaa Xaa Val     
#        45                                                               
- Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp Al - #a Pro Leu Ser Ser Xaa     
#    60                                                                   
- Pro Ser Xaa Ala Leu Xaa Leu Ala Gly Xaa Le - #u Ser Gln Leu His Ser     
#80                                                                       
- Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Al - #a Leu Glu Gly Ile Ser     
#                95                                                       
- Pro Glu Leu Gly Pro Thr Leu Xaa Thr Leu Gl - #n Xaa Asp Val Ala Asp     
#           110                                                           
- Phe Ala Xaa Thr Ile Trp Gln Gln Met Glu Xa - #a Xaa Gly Met Ala Pro     
#       125                                                               
- Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Al - #a Phe Ala Ser Ala Xaa     
#   140                                                                   
- Gln Xaa Xaa Ala Gly Gly Val Leu Val Ala Se - #r Xaa Leu Gln Xaa Phe     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Leu Xaa Xaa Ser Tyr Arg Val Leu Xaa Xaa Le - #u Ala Gln Pro             
#               170                                                       
- (2) INFORMATION FOR SEQ ID NO:2:                                        
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 133 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: protein                                         
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 17                                                
#/note= "Xaa at position 17 is Ser,                                       
               Lys, Gly, - # Asp, Met, Gln, or Arg;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 18                                                
#/note= "Xaa at position 18 is Asn,                                       
               His, Leu, - # Ile, Phe, Arg, or Gln;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 19                                                
#/note= "Xaa at position 19 is Met,                                       
               Phe, Ile, - # Arg, Gly, Ala, or Cys;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 20                                                
#/note= "Xaa at position 20 is Ile,                                       
               Cys, Gln, - # Glu, Arg, Pro, or Ala;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 21                                                
#/note= "Xaa at position 21 is Asp,                                       
#Val;"         Phe, Lys, - # Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or    
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 22                                                
#/note= "Xaa at position 22 is Glu,                                       
#Gly;"         Trp, Pro, - # Ser, Ala, His, Asp, Asn, Gln, Leu, Val or    
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 23                                                
#/note= "Xaa at position 23 is Ile,                                       
               Val, Ala, - # Gly, Trp, Lys, Phe, Leu, Ser, or Arg;"       
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 24                                                
#/note= "Xaa at position 24 is Ile,                                       
               Gly, Val, - # Arg, Ser, Phe, Leu;"                         
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 25                                                
#/note= "Xaa at position 25 is Thr,                                       
               His, Gly, - # Gln, Arg, Pro, or Ala;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 26                                                
#/note= "Xaa at position 26 is His,                                       
               Thr, Phe, - # Gly, Arg, Ala, Trp;"                         
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 27                                                
#/note= "Xaa at position 27 is Leu,                                       
               Gly, Arg, - # Thr, Ser, or Ala;"                           
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 28                                                
#/note= "Xaa at position 28 is Lys,                                       
               Arg, Leu, - # Gln, Gly, Pro, Val or Trp;"                  
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 29                                                
#/note= "Xaa at position 29 is Gln,                                       
               Asn, Leu, - # Pro, Arg, or Val;"                           
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 30                                                
#/note= "Xaa at position 30 is Pro,                                       
               His, Thr, - # Gly, Asp, Gln, Ser, Leu, or L..."            
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 31                                                
#/note= "Xaa at position 31 is Pro,                                       
               Asp, Gly, - # Ala, Arg, Leu, or Gln;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 32                                                
#/note= "Xaa at position 32 is Leu,                                       
               Val, Arg, - # Gln, Asn, Gly, Ala, or Glu;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 33                                                
#/note= "Xaa at position 33 is Pro,                                       
               Leu, Gln, - # Ala, Thr, or Glu;"                           
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 34                                                
#/note= "Xaa at position 34 is Leu,                                       
               Val, Gly, - # Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile  
- # or Met;"                                                              
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 35                                                
#/note= "Xaa at position 35 is Leu,                                       
               Ala, Gly, - # Asn, Pro, Gln, or Val;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 36                                                
#/note= "Xaa at position 36 is Asp,                                       
#Val;"         Leu, or                                                    
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 37                                                
#/note= "Xaa at position 37 is Phe,                                       
               Ser, Pro, - # Trp, or Ile;"                                
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 38                                                
#/note= "Xaa at position 38 is Asn,                                       
               or Ala;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 40                                                
#/note= "Xaa at position 40 is Leu,                                       
#Arg;"         Trp, or                                                    
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 41                                                
#/note= "Xaa at position 41 is Asn,                                       
               Cys, Arg, - # Leu, His, Met, or pro;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 42                                                
#/note= "Xaa at position 42 is Gly,                                       
               Asp, Ser, - # Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr  
- #, Ile, Met                                                             
               or Ala;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 43                                                
#/note= "Xaa at position 43 is Glu,                                       
               Asn, Tyr, - # Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly  
- #, or Ser;"                                                             
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 44                                                
#/note= "Xaa at position 44 is Asp,                                       
               Ser, Leu, - # Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala  
- # or Pro;"                                                              
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 45                                                
#/note= "Xaa at position 45 is Gln,                                       
               Pro, Phe, - # Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg  
- #, Ser, Ala,                                                            
#or His;"      Ile, Glu                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 46                                                
#/note= "Xaa at position 46 is Asp,                                       
               Phe, Ser, - # Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr  
- #, Ile, Val                                                             
               or Gly;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 47                                                
#/note= "Xaa at position 47 is Ile,                                       
               Gly, Val, - # Ser, Arg, Pro, or His;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 48                                                
#/note= "Xaa at position 48 is Leu,                                       
               Ser, Cys, - # Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met  
- #, Val or                                                               
               Asn;"                                                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 49                                                
#/note= "Xaa at position 49 is Met,                                       
               Arg, Ala, - # Gly, Pro, Asn, His, or Asp;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 50                                                
#/note= "Xaa at position 50 is Glu,                                       
               Leu, Thr, - # Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His  
- #, Phe, Met                                                             
               or Gln;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 51                                                
#/note= "Xaa at position 51 is Asn,                                       
               Arg, Met, - # Pro, Ser, Thr, or his;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 52                                                
#/note= "Xaa at position 52 is Asn,                                       
               His, Arg, - # Leu, Gly, Ser, or Thr;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 53                                                
#/note= "Xaa at position 53 is Leu,                                       
               Thr, Ala, - # Gly, Glu, Pro, Lys, Ser, or M..."            
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 54                                                
#/note= "Xaa at position 54 is Arg,                                       
#Leu;"         Asp, Ile, - # Ser, Val, Thr, Gln, Asn, Lys, His, Ala or    
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 55                                                
#/note= "Xaa at position 55 is Arg,                                       
               Thr, Val, - # Ser, Leu, or Gly;"                           
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 56                                                
#/note= "Xaa at position 56 is Pro,                                       
               Gly, Cys, - # Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe  
- #, Leu, Val                                                             
               or Lys;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 57                                                
#/note= "Xaa at position 57 is Asn                                        
               or Gly;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 58                                                
#/note= "Xaa at position 58 is Leu,                                       
               Ser, Asp, - # Arg, Gln, Val, or Cys;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 59                                                
#/note= "Xaa at position 59 is Glu,                                       
               Tyr, His, - # Leu, Pro, or Arg;"                           
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 60                                                
#/note= "Xaa at position 60 is Ala,                                       
               Ser, Pro, - # Tyr, Asn, or Thr;"                           
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 61                                                
#/note= "Xaa at position 61 is Phe,                                       
               Asn, Glu, - # Pro, Lys, Arg, or Ser;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 62                                                
#/note= "Xaa at position 62 is Asn,                                       
               His, Val, - # Arg, Pro, Thr, Asp, or Ile;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 63                                                
#/note= "Xaa at position 63 is Arg,                                       
               Tyr, Trp, - # Lys, Ser, His, Pro, or Val;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 64                                                
#/note= "Xaa at position 64 is Ala,                                       
               Asn, Pro, - # Ser, or Lys;"                                
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 65                                                
#/note= "Xaa at position 65 is Val,                                       
               Thr, Pro, - # His, Leu, Phe, or Ser;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 66                                                
#/note= "Xaa at position 66 is Lys,                                       
               Ile, Arg, - # Val, Asn, Glu, or Ser;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 67                                                
#/note= "Xaa at postion 67 is Ser,                                        
               Ala, Phe, - # Val, Gly, Asn, Ile, Pro, or His;"            
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 68                                                
#/note= "Xaa at position 68 is Leu,                                       
               Val, Trp, - # Ser, Ile, Phe, Thr, or His;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 69                                                
#/note= "Xaa at position 69 is Gln,                                       
               Ala, Pro, - # Thr, Glu, Arg, Trp, Gly, or L..."            
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 70                                                
#/note= "Xaa at position 70 is Asn,                                       
               Leu, Val, - # Trp, pro, or Ala;"                           
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 71                                                
#/note= "Xaa at position 71 is Ala,                                       
               Met, Leu, - # Pro, Arg, Glu, Thr, Gln, Trp, or Asn;"       
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 72                                                
#/note= "Xaa at position 72 is Ser,                                       
               Glu, Met, - # Ala, His, Asn, Arg, or Asp;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 73                                                
#/note= "Xaa at position 73 is Ala,                                       
               Glu, Asp, - # Leu, Ser, Gly, Thr, or Arg;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 74                                                
#/note= "Xaa at position 74 is Ile,                                       
               Met, Thr, - # Pro, Arg, Gly, Ala;"                         
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 75                                                
#/note= "Xaa at position 75 is Glu,                                       
               Lys, Gly, - # Asp, Pro, Trp, Arg, Ser, Gln, or Leu;"       
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 76                                                
#/note= "Xaa at position 76 is Ser,                                       
               Val, Ala, - # Asn, Trp, Glu, Pro, Gly, or A..."            
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 77                                                
#/note= "Xaa at position 77 is Ile,                                       
               Ser, Arg, - # Thr, or Leu;"                                
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 78                                                
#/note= "Xaa at position 78 is Leu,                                       
               Ala, Ser, - # Glu, Phe, Gly, or Arg;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 79                                                
#/note= "Xaa at position 79 is Lys,                                       
               Thr, Asn, - # Met, Arg, Ile, Gly, or Asp;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 80                                                
#/note= "Xaa position at 80 is Asn,                                       
               Trp, Val, - # Gly, Thr, Leu, Glu, or Arg;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 81                                                
#/note= "Xaa at position 81 is Leu,                                       
               Gln, Gly, - # Ala, Trp, Arg, Val, or Lys;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 82                                                
#/note= "Xaa at position 82 is Leu,                                       
               Gln, Lys, - # Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala  
- #, Tyr, Phe,                                                            
#or Val;"      Ile, Met                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 83                                                
#/note= "Xaa at position 83 is Pro,                                       
               Ala, Thr, - # Trp, Arg, or Met;"                           
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 84                                                
#/note= "Xaa at position 84 is Cys,                                       
               Glu, Gly, - # Arg, Met, or Val;"                           
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 85                                                
#/note= "Xaa at position 85 is Leu,                                       
               Asn, Val, - # or Gln;"                                     
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 86                                                
#/note= "Xaa at position 86 is Pro,                                       
               Cys, Arg, - # Ala, or Lys;"                                
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 87                                                
#/note= "Xaa at position 87 is Leu,                                       
               Ser, Trp, - # or Gly;"                                     
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 88                                                
#/note= "Xaa at position 88 is Ala,                                       
               Lys, Arg, - # Val, or Trp;"                                
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 89                                                
#/note= "Xaa at position 89 is Thr,                                       
               Asp, Cys, - # Leu, Val, Glu, His, Asn, or S..."            
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 90                                                
#/note= "Xaa at position 90 is Ala,                                       
               Pro, Ser, - # Thr, Gly, Asp, Ile, or ,Met;"                
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 91                                                
#/note= "Xaa at position 91 is Ala,                                       
               Pro, Ser, - # Thr, Phe, Leu, Asp, or His;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 92                                                
#/note= "Xaa at position 92 is Pro,                                       
               Phe, Arg, - # Ser, Lys, His, Ala, Gly, Ile or Leu;"        
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 93                                                
#/note= "Xaa at position 93 is Thr,                                       
               Asp, Ser, - # Asn, Pro, Ala, Leu, or Arg;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 94                                                
#/note= "Xaa at position 94 is Arg,                                       
               Ile, Ser, - # Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;"  
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 95                                                
#/note= "Xaa at position 95 is His,                                       
               Gln, Pro, - # Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala  
- #, Trp, Phe,                                                            
#Tyr;"         Ile, or                                                    
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 96                                                
#/note= "Xaa at position 96 is Pro,                                       
               Lys, Tyr, - # Gly, Ile, or Thr;"                           
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 97                                                
#/note= "Xaa at position 97 is Ile,                                       
               Val, Lys, - # Ala, or Asn;"                                
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 98                                                
#/note= "Xaa at position 98 is His,                                       
               Ile, Asn, - # Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met  
- #, Val, Lys,                                                            
               Arg, Tyr, - # or Pro;"                                     
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 99                                                
#/note= "Xaa at position 99 is Ile,                                       
               Leu, Arg, - # Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;"  
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 100                                               
#/note= "Xaa at position 100 is Lys,                                      
               Tyr, Leu, - # His, Arg, Ile, Ser, Gln, or ..."             
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 101                                               
#/note= "Xaa at position is Asp,                                          
               Pro, Met, - # Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala  
- #, Gly, Ile,                                                            
#Gln;"         Leu, or                                                    
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 102                                               
#/note= "Xaa at position 102 is Gly,                                      
               Leu, Glu, - # Lys, Ser, Tyr, or Pro;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 103                                               
#/note= "Xaa at position 103 is Asp,                                      
               or Ser;"                                                   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 104                                               
#/note= "Xaa at position 104 is Trp,                                      
               Val, Cys, - # Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe  
- #, or Gly;"                                                             
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 105                                               
#/note= "Xaa at position 105 is Asn,                                      
               Pro, Ala, - # Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp  
- #, or His;"                                                             
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 106                                               
#/note= "Xaa at position 106 is Glu,                                      
               Ser, Ala, - # Lys, Thr, Ile, Gly, or Pro;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 108                                               
#/note= "Xaa at position 108 is Arg,                                      
               Lys, Asp, - # Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;"   
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 109                                               
#/note= "Xaa at position 109 is Arg,                                      
               Thr, Pro, - # Glu, Tyr, Leu, Ser, or Gly;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 110                                               
#/note= "Xaa at position 110 is Lys,                                      
               Ala, Asn, - # Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp;"  
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 111                                               
#/note= "Xaa at position 111 is Leu,                                      
               Ile, Arg, - # Asp, or Met;"                                
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 112                                               
#/note= "Xaa at position 112 is Thr,                                      
               Val, Gln, - # Tyr, Glu, His, Ser, or Phe;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 113                                               
#/note= "Xaa at position 113 is Phe,                                      
               Ser, Cys, - # His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val  
- # or Asn;"                                                              
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 114                                               
#/note= "Xaa at position 114 is Tyr,                                      
               Cys, His, - # Ser, Trp, Arg, or Leu;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 115                                               
#/note= "Xaa at position 115 is Leu,                                      
               Asn, Val, - # Pro, Arg, Ala, His, Thr, Trp, or Met;"       
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 116                                               
#/note= "Xaa at position 116 is Lys,                                      
               Leu, Pro, - # Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn  
- #, His, Ala,                                                            
               Tyr, Phe, - # Gln, or Ile;"                                
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 117                                               
#/note= "Xaa at position 117 is Thr,                                      
               Ser, Asn, - # Ile, Trp, Lys, or Pro;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 118                                               
#/note= "Xaa at position 118 is Leu,                                      
               Ser, Pro, - # Ala, Glu, Cys, Asp, or Tyr;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 119                                               
#/note= "Xaa at position 119 is Glu,                                      
               Ser, Lys, - # Pro, leu, Thr, Tyr, or Arg;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 120                                               
#/note= "Xaa at position 120 is Asn,                                      
               Ala, Pro, - # Leu, His, Val, or Gln;"                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 121                                               
#/note= "Xaa at position 121 is Ala,                                      
               Ser, Ile, - # Asn, Pro, Lys, Asp, or Gly;"                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 122                                               
#/note= "Xaa at position 122 is Gln,                                      
               Ser, Met, - # Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;"  
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 123                                               
#/note= "Xaa at position 123 is Ala,                                      
               Met, Glu, - # His, Ser, Pro, Tyr, or Leu;"                 
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:                             
- Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Th - #r Ser Trp Val Asn Cys     
#                15                                                       
- Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xa - #a Xaa Xaa Xaa Xaa Xaa     
#            30                                                           
- Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xa - #a Xaa Xaa Xaa Xaa Xaa     
#        45                                                               
- Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xa - #a Xaa Xaa Xaa Xaa Xaa     
#    60                                                                   
- Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xa - #a Xaa Xaa Xaa Xaa Xaa     
#80                                                                       
- Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xa - #a Xaa Xaa Xaa Xaa Xaa     
#                95                                                       
- Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ph - #e Xaa Xaa Xaa Xaa Xaa     
#           110                                                           
- Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xa - #a Gln Gln Thr Thr Leu     
#       125                                                               
- Ser Leu Ala Ile Phe                                                     
    130                                                                   
- (2) INFORMATION FOR SEQ ID NO:3:                                        
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 332 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: protein                                         
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 112                                               
#/note= "position 112 is deleted or                                       
               Leu, Ala, - # Val, Ile, Pro, Phe, Trp, or M..."            
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 113                                               
#/note= "position 113 is deleted or                                       
               Pro, Phe, - # Ala, Leu, Ile, Trp, or Met"                  
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 114                                               
#/note= "position 114 is deleted or                                       
               Pro, Phe, - # Ala, Val, Leu, Ile, Trp or Met"              
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 115                                               
#/note= "position 115 is deleted or                                       
               Gln, Gly, - # Ser, Thr, Tyr or Asn"                        
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3:                             
- Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Va - #l Leu Ser Lys Leu Leu     
#                15                                                       
- Arg Asp Ser His Val Leu His Ser Arg Leu Se - #r Gln Cys Pro Glu Val     
#            30                                                           
- His Pro Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
#        45                                                               
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#    60                                                                   
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#80                                                                       
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#                95                                                       
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Xaa     
#           110                                                           
- Xaa Xaa Xaa Gly Arg Thr Thr Ala His Lys As - #p Pro Asn Ala Ile Phe     
#       125                                                               
- Leu Ser Phe Gln His Leu Leu Arg Gly Lys Va - #l Arg Phe Leu Met Leu     
#   140                                                                   
- Val Gly Gly Ser Thr Leu Cys Val Arg Arg Al - #a Pro Pro Thr Thr Ala     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Val Pro Ser Arg Thr Ser Leu Val Leu Thr Le - #u Asn Glu Leu Pro Asn     
#               175                                                       
- Arg Thr Ser Gly Leu Leu Glu Thr Asn Phe Th - #r Ala Ser Ala Arg Thr     
#           190                                                           
- Thr Gly Ser Gly Leu Leu Lys Trp Gln Gln Gl - #y Phe Arg Ala Lys Ile     
#       205                                                               
- Pro Gly Leu Leu Asn Gln Thr Ser Arg Ser Le - #u Asp Gln Ile Pro Gly     
#   220                                                                   
- Tyr Leu Asn Arg Ile His Glu Leu Leu Asn Gl - #y Thr Arg Gly Leu Phe     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Pro Gly Pro Ser Arg Arg Thr Leu Gly Ala Pr - #o Asp Ile Ser Ser Gly     
#               255                                                       
- Thr Ser Asp Thr Gly Ser Leu Pro Pro Asn Le - #u Gln Pro Gly Tyr Ser     
#           270                                                           
- Pro Ser Pro Thr His Pro Pro Thr Gly Gln Ty - #r Thr Leu Phe Pro Leu     
#       285                                                               
- Pro Pro Thr Leu Pro Thr Pro Val Val Gln Le - #u His Pro Leu Leu Pro     
#   300                                                                   
- Asp Pro Ser Ala Pro Thr Pro Thr Pro Thr Se - #r Pro Leu Leu Asn Thr     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Ser Tyr Thr His Ser Gln Asn Leu Ser Gln Gl - #u Gly                     
#               330                                                       
- (2) INFORMATION FOR SEQ ID NO:4:                                        
-      (i) SEQUENCE CHARACTERISTICS:                                      
          (A) LENGTH: 5 base p - #airs                                    
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4:                             
#             5                                                           
- (2) INFORMATION FOR SEQ ID NO:5:                                        
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 3 amino                                             
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Peptide                                           
          (B) LOCATION: 1                                                 
#/note= "where x=(glyglyglyglyser)n                                       
               and where - # n is an interger"                            
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5:                             
- Xaa Ala Ala                                                             
- (2) INFORMATION FOR SEQ ID NO:6:                                        
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 3 amino                                             
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Peptide                                           
          (B) LOCATION: 1                                                 
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Peptide                                           
          (B) LOCATION: 1                                                 
#/note= "where XaaR INFORMATION:                                          
               =(glyglyg - #lyglyglyser)n and where n is an integer"      
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6:                             
- Xaa Ala Ala                                                             
1                                                                         
- (2) INFORMATION FOR SEQ ID NO:7:                                        
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 3 amino                                             
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Peptide                                           
          (B) LOCATION: 1                                                 
#/note= "where xaa = (gly(n)ser)m                                         
               and where - # n is an integer and m is an int..."          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7:                             
- Xaa Ala Ala                                                             
1                                                                         
- (2) INFORMATION FOR SEQ ID NO:8:                                        
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 3 amino                                             
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Peptide                                           
          (B) LOCATION: 1                                                 
#/note= "where Xaa=(alaglyser)n and                                       
#is an integer"where n                                                    
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8:                             
- Xaa Ala Ala                                                             
1                                                                         
- (2) INFORMATION FOR SEQ ID NO:9:                                        
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 36 amino                                            
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: protein                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9:                             
- Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gl - #y Ser Glu Gly Gly Gly     
#                15                                                       
- Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Se - #r Glu Gly Gly Gly Ser     
#            30                                                           
- Gly Gly Gly Ser                                                         
        35                                                                
- (2) INFORMATION FOR SEQ ID NO:10:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 24 amino                                            
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10:                            
- Ile Ser Glu Pro Ser Gly Pro Ile Ser Thr Il - #e Asn Pro Ser Pro Pro     
#                15                                                       
- Ser Lys Glu Ser His Lys Ser Pro                                         
            20                                                            
- (2) INFORMATION FOR SEQ ID NO:11:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 28 amino                                            
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11:                            
- Ile Glu Gly Arg Ile Ser Glu Pro Ser Gly Pr - #o Ile Ser Thr Ile Asn     
#                15                                                       
- Pro Ser Pro Pro Ser Lys Glu Ser His Lys Se - #r Pro                     
#            25                                                           
- (2) INFORMATION FOR SEQ ID NO:12:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 4 amino                                             
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12:                            
- Gly Gly Gly Ser                                                         
1                                                                         
- (2) INFORMATION FOR SEQ ID NO:13:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 45 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13:                            
#45                CNGC NCCNCCTGCT TGTGCACTCC GAGTC                       
- (2) INFORMATION FOR SEQ ID NO:14:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 30 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14:                            
#           30     ACGC AGAGGGTGGA                                        
- (2) INFORMATION FOR SEQ ID NO:15:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 33 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15:                            
#         33       CGCA GAGGGTGGAC CCT                                    
- (2) INFORMATION FOR SEQ ID NO:16:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 10 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16:                            
#        10                                                               
- (2) INFORMATION FOR SEQ ID NO:17:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 10 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17:                            
#        10                                                               
- (2) INFORMATION FOR SEQ ID NO:18:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 13 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18:                            
#      13                                                                 
- (2) INFORMATION FOR SEQ ID NO:19:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 13 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19:                            
#      13                                                                 
- (2) INFORMATION FOR SEQ ID NO:20:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 22 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20:                            
#                 22GGC AA                                                
- (2) INFORMATION FOR SEQ ID NO:21:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 22 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21:                            
#                 22CGC CG                                                
- (2) INFORMATION FOR SEQ ID NO:22:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 27 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22:                            
#             27   ACCC TTTGCCT                                           
- (2) INFORMATION FOR SEQ ID NO:23:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 29 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23:                            
#            29    ACTG GCTCAGTCT                                         
- (2) INFORMATION FOR SEQ ID NO:24:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 27 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24:                            
#             27   CACC TGTCCTG                                           
- (2) INFORMATION FOR SEQ ID NO:25:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 29 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25:                            
#            29    GAAC CTCTGGGCA                                         
- (2) INFORMATION FOR SEQ ID NO:26:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 27 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26:                            
#             27   TGCC TGCTGTG                                           
- (2) INFORMATION FOR SEQ ID NO:27:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 29 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27:                            
#            29    TAGG CAAAGGGTG                                         
- (2) INFORMATION FOR SEQ ID NO:28:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 30 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28:                            
#           30     ACTT TAGCTTGGGA                                        
- (2) INFORMATION FOR SEQ ID NO:29:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 29 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29:                            
#            29    GCAG GACAGGTGT                                         
- (2) INFORMATION FOR SEQ ID NO:30:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 27 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30:                            
#             27   GCTT GGGAGAA                                           
- (2) INFORMATION FOR SEQ ID NO:31:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 29 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31:                            
#            29    CAGG CAGCAGGAC                                         
- (2) INFORMATION FOR SEQ ID NO:32:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 27 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32:                            
#             27   GGAA AACCCAG                                           
- (2) INFORMATION FOR SEQ ID NO:33:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 29 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33:                            
#            29    TAAA GTCCACAGC                                         
- (2) INFORMATION FOR SEQ ID NO:34:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 27 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34:                            
#             27   CTTG CCTCTCA                                           
- (2) INFORMATION FOR SEQ ID NO:35:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 29 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35:                            
#            29    GTCC CCGTGCTGC                                         
- (2) INFORMATION FOR SEQ ID NO:36:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 27 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36:                            
#             27   AGCT TCCTCCA                                           
- (2) INFORMATION FOR SEQ ID NO:37:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 29 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:37:                            
#            29    GGCT CTGCAGGGC                                         
- (2) INFORMATION FOR SEQ ID NO:38:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 27 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38:                            
#             27   CCAC AGCTCAC                                           
- (2) INFORMATION FOR SEQ ID NO:39:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 30 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:39:                            
#           30     GAGG AAGCTGGGTT                                        
- (2) INFORMATION FOR SEQ ID NO:40:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 30 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:40:                            
#           30     AGGA TCCCAATGCC                                        
- (2) INFORMATION FOR SEQ ID NO:41:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 29 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:41:                            
#            29    TCCT GCGCTGTGG                                         
- (2) INFORMATION FOR SEQ ID NO:42:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 30 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:42:                            
#           30     ATGC CATCTTCCTG                                        
- (2) INFORMATION FOR SEQ ID NO:43:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 29 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:43:                            
#            29    GAGC TGTGGTCCT                                         
- (2) INFORMATION FOR SEQ ID NO:44:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 30 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:44:                            
#           30     TCCT GAGCTTCCAA                                        
- (2) INFORMATION FOR SEQ ID NO:45:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 32 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:45:                            
#          32      GATC CTTGTGAGCT GT                                     
- (2) INFORMATION FOR SEQ ID NO:46:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 83 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "SYNTHETIC"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46:                            
- AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA GAACGCGCAG GC - #TCAACAGT   
  60                                                                      
#                83AGGC TCC                                               
- (2) INFORMATION FOR SEQ ID NO:47:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 83 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47:                            
- CCGGGGAGCC TCCACCGCCC TCTACGTACT GTTGAGCCTG CGCGTTCTCC AA - #GGTTTTCA   
  60                                                                      
#                83ACGA CGG                                               
- (2) INFORMATION FOR SEQ ID NO:48:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 59 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:48:                            
- GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT CTAACTGCTC TA - #TAATGAT    
  59                                                                      
- (2) INFORMATION FOR SEQ ID NO:49:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 56 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:49:                            
- CGATCATTAT AGAGCAGTTA GAGCCACCAC CCTGTTGTTC CTGCGCTTGC TC - #AAGG       
  56                                                                      
- (2) INFORMATION FOR SEQ ID NO:50:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 80 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:50:                            
- GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT CTGGCGGTGG CA - #GCGGCGGC   
  60                                                                      
# 80               TAAT                                                   
- (2) INFORMATION FOR SEQ ID NO:51:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 80 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:51:                            
- CGATCATTAT AGAGCAGTTA GAACCGCCGC CGCTGCCACC GCCAGAGCCA CC - #ACCCTGTT   
  60                                                                      
# 80               AAGG                                                   
- (2) INFORMATION FOR SEQ ID NO:52:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 30 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:52:                            
#           30     GGAC CCGAACAACC                                        
- (2) INFORMATION FOR SEQ ID NO:53:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 28 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:53:                            
#             28   GGTG CAGGTGGT                                          
- (2) INFORMATION FOR SEQ ID NO:54:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 32 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:54:                            
#          32      TGCA TCAGGTATTG AG                                     
- (2) INFORMATION FOR SEQ ID NO:55:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 28 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:55:                            
#             28   AAGT TCTTGACA                                          
- (2) INFORMATION FOR SEQ ID NO:56:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 32 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:56:                            
#          32      ACCC TCTCGACATC CA                                     
- (2) INFORMATION FOR SEQ ID NO:57:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 28 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:57:                            
#             28   GTGG CAGAGGGC                                          
- (2) INFORMATION FOR SEQ ID NO:58:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 32 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:58:                            
#          32      AGGT GACTGGCAAG AA                                     
- (2) INFORMATION FOR SEQ ID NO:59:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 28 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:59:                            
#             28   ATGA TGATTGGA                                          
- (2) INFORMATION FOR SEQ ID NO:60:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 54 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:60:                            
- GCTCTGAGAG CCGCCAGAGC CGCCAGAGGG CTGCGCAAGG TGGCGTAGAA CG - #CG         
  54                                                                      
- (2) INFORMATION FOR SEQ ID NO:61:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 54 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:61:                            
- CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AG - #AG         
  54                                                                      
- (2) INFORMATION FOR SEQ ID NO:62:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 18 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:62:                            
#  18              CG                                                     
- (2) INFORMATION FOR SEQ ID NO:63:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 21 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:63:                            
#21                CCAG C                                                 
- (2) INFORMATION FOR SEQ ID NO:64:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 32 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:64:                            
#          32      CAAG CTGTGCCACC CC                                     
- (2) INFORMATION FOR SEQ ID NO:65:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 36 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:65:                            
#       36         GGTG GCACACAGCT TCTCCT                                 
- (2) INFORMATION FOR SEQ ID NO:66:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 32 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:66:                            
#          32      CGAG TTGGGTCCCA CC                                     
- (2) INFORMATION FOR SEQ ID NO:67:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 36 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:67:                            
#       36         GGAT ATCCCTTCCA GGGCCT                                 
- (2) INFORMATION FOR SEQ ID NO:68:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 32 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:68:                            
#          32      GGCC CCTGCCCTGC AG                                     
- (2) INFORMATION FOR SEQ ID NO:69:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 36 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:69:                            
#       36         TCCC AGTTCTTCCA TCTGCT                                 
- (2) INFORMATION FOR SEQ ID NO:70:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 32 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:70:                            
#          32      CCAG GGTGCCATGC CG                                     
- (2) INFORMATION FOR SEQ ID NO:71:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 36 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:71:                            
#       36         GGGC TGCAGGGCAG GGGCCA                                 
- (2) INFORMATION FOR SEQ ID NO:72:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 36 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:72:                            
#       36         GGGC TGCAGGGCAG GGGCCA                                 
- (2) INFORMATION FOR SEQ ID NO:73:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 36 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:73:                            
#       36         GGCG AAGGCCGGCA TGGCAC                                 
- (2) INFORMATION FOR SEQ ID NO:74:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 21 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:74:                            
#21                GCTC C                                                 
- (2) INFORMATION FOR SEQ ID NO:75:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 25 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:75:                            
#               25 GCCC TCTAC                                             
- (2) INFORMATION FOR SEQ ID NO:76:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 53 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:76:                            
- TTCTACGCCA CCTTGCGCAG CCCGGCGGCG GCTCTGACAT GTCTACACCA TT - #G          
  53                                                                      
- (2) INFORMATION FOR SEQ ID NO:77:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 53 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:77:                            
- CAATGGTGTA GACATGTCAG AGCCGCCGCC GGGCTGCGCA AGGTGGCGTA GA - #A          
  53                                                                      
- (2) INFORMATION FOR SEQ ID NO:78:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 439 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:78:                            
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
#439               TGT                                                    
- (2) INFORMATION FOR SEQ ID NO:79:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 465 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:79:                            
- TCCCCAGCTC CACCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TG - #ACTCCCAT   
  60                                                                      
- GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC AC - #CTGTCCTG   
 120                                                                      
- CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GA - #CCAAGGCA   
 180                                                                      
- CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC AC - #GGGGACAA   
 240                                                                      
- CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CC - #GTCTCCTC   
 300                                                                      
- CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GA - #CCACAGCT   
 360                                                                      
- CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AA - #AGGTGCGT   
 420                                                                      
#                 465GG GTCCACCCTC TGCGTCAGGG AATTC                       
- (2) INFORMATION FOR SEQ ID NO:80:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:80:                            
- TCCCCAGCTC CACCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TG - #ACTCCCAT   
  60                                                                      
- GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC AC - #CTGTCCTG   
 120                                                                      
- CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GA - #CCAAGGCA   
 180                                                                      
- CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC AC - #GGGGACAA   
 240                                                                      
- CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CC - #GTCTCCTC   
 300                                                                      
- CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GA - #CCACAGCT   
 360                                                                      
- CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AA - #AGGTGCGT   
 420                                                                      
- TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGGG AATTCGGCGG CA - #ACATGGCG   
 480                                                                      
- TCTCCCGCTC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TG - #ACTCCCAT   
 540                                                                      
- GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC AC - #CTGTCCTG   
 600                                                                      
- CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GA - #CCAAGGCA   
 660                                                                      
- CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC AC - #GGGGACAA   
 720                                                                      
- CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CC - #GTCTCCTC   
 780                                                                      
- CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGGGCAGGA CCACAGCTCA CA - #AGGATCCC   
 840                                                                      
- AATGCCATCT TCCTGAGCTT CCAACACCTG CTCCGAGGAA AGGTGCGTTT CC - #TGATGCTT   
 900                                                                      
#            927   TCTG CGTCAGG                                           
- (2) INFORMATION FOR SEQ ID NO:81:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 936 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:81:                            
- TCCCCAGCTC CACCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TG - #ACTCCCAT   
  60                                                                      
- GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC AC - #CTGTCCTG   
 120                                                                      
- CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GA - #CCAAGGCA   
 180                                                                      
- CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC AC - #GGGGACAA   
 240                                                                      
- CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CC - #GTCTCCTC   
 300                                                                      
- CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GA - #CCACAGCT   
 360                                                                      
- CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AA - #AGGTGCGT   
 420                                                                      
- TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGGG AATTCGGCAA CA - #TGGCGTCT   
 480                                                                      
- CCCGCTCCGC CTGCTTGTGA CCTCCGAGTC CTCAGTAAAC TGCTTCGTGA CT - #CCCATGTC   
 540                                                                      
- CTTCACAGCA GACTGAGCCA GTGCCCAGAG GTTCACCCTT TGCCTACACC TG - #TCCTGCTG   
 600                                                                      
- CCTGCTGTGG ACTTTAGCTT GGGAGAATGG AAAACCCAGA TGGAGGAGAC CA - #AGGCACAG   
 660                                                                      
- GACATTCTGG GAGCAGTGAC CCTTCTGCTG GAGGGAGTGA TGGCAGCACG GG - #GACAACTG   
 720                                                                      
- GGACCCACTT GCCTCTCATC CCTCCTGGGG CAGCTTTCTG GACAGGTCCG TC - #TCCTCCTT   
 780                                                                      
- GGGGCCCTGC AGAGCCTCCT TGGAACCCAG CTTCCTCCAC AGGGCAGGAC CA - #CAGCTCAC   
 840                                                                      
- AAGGATCCCA ATGCCATCTT CCTGAGCTTC CAACACCTGC TCCGAGGAAA GG - #TGCGTTTC   
 900                                                                      
#      936         GGTC CACCCTCTGC GTCAGG                                 
- (2) INFORMATION FOR SEQ ID NO:82:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 939 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:82:                            
- TCCCCAGCTC CACCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TG - #ACTCCCAT   
  60                                                                      
- GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC AC - #CTGTCCTG   
 120                                                                      
- CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GA - #CCAAGGCA   
 180                                                                      
- CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC AC - #GGGGACAA   
 240                                                                      
- CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CC - #GTCTCCTC   
 300                                                                      
- CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GA - #CCACAGCT   
 360                                                                      
- CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AA - #AGGTGCGT   
 420                                                                      
- TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGGG AATTCGGCGG CA - #ACATGGCG   
 480                                                                      
- TCTCCCGCTC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TG - #ACTCCCAT   
 540                                                                      
- GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC AC - #CTGTCCTG   
 600                                                                      
- CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GA - #CCAAGGCA   
 660                                                                      
- CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC AC - #GGGGACAA   
 720                                                                      
- CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CC - #GTCTCCTC   
 780                                                                      
- CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GA - #CCACAGCT   
 840                                                                      
- CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AA - #AGGTGCGT   
 900                                                                      
#   939            GAGG GTCCACCCTC TGCGTCAGG                              
- (2) INFORMATION FOR SEQ ID NO:83:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 948 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:83:                            
- TCCCCAGCGC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TG - #ACTCCCAT   
  60                                                                      
- GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC AC - #CTGTCCTG   
 120                                                                      
- CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GA - #CCAAGGCA   
 180                                                                      
- CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC AC - #GGGGACAA   
 240                                                                      
- CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CC - #GTCTCCTC   
 300                                                                      
- CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GA - #CCACAGCT   
 360                                                                      
- CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AA - #AGGTGCGT   
 420                                                                      
- TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGGG AATTCGGCGG CA - #ACGGCGGC   
 480                                                                      
- AACATGGCGT CCCCAGCGCC GCCTGCTTGT GACCTCCGAG TCCTCAGTAA AC - #TGCTTCGT   
 540                                                                      
- GACTCCCATG TCCTTCACAG CAGACTGAGC CAGTGCCCAG AGGTTCACCC TT - #TGCCTACA   
 600                                                                      
- CCTGTCCTGC TGCCTGCTGT GGACTTTAGC TTGGGAGAAT GGAAAACCCA GA - #TGGAGGAG   
 660                                                                      
- ACCAAGGCAC AGGACATTCT GGGAGCAGTG ACCCTTCTGC TGGAGGGAGT GA - #TGGCAGCA   
 720                                                                      
- CGGGGACAAC TGGGACCCAC TTGCCTCTCA TCCCTCCTGG GGCAGCTTTC TG - #GACAGGTC   
 780                                                                      
- CGTCTCCTCC TTGGGGCCCT GCAGAGCCTC CTTGGAACCC AGCTTCCTCC AC - #AGGGCAGG   
 840                                                                      
- ACCACAGCTC ACAAGGATCC CAATGCCATC TTCCTGAGCT TCCAACACCT GC - #TCCGAGGA   
 900                                                                      
#               948TGCT TGTAGGAGGG TCCACCCTCT GCGTCAGG                    
- (2) INFORMATION FOR SEQ ID NO:84:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 688 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:84:                            
- CATGGCTAAC TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA GA - #CCACCTGC   
  60                                                                      
- ACCTTTGCTG GACCCGAACA ACCTCAATGA CGAAGACGTC TCTATCCTGA TG - #GACCGAAA   
 120                                                                      
- CCTTCGACTT CCAAACCTGG AGAGCTTCGT AAGGGCTGTC AAGAACTTAG AA - #AATGCATC   
 180                                                                      
- AGGTATTGAG GCAATTCTTC GTAATCTCCA ACCATGTCTG CCCTCTGCCA CG - #GCCGCACC   
 240                                                                      
- CTCTCGACAT CCAATCATCA TCAAGGCAGG TGACTGGCAA GAATTCCGGG AA - #AAACTGAC   
 300                                                                      
- GTTCTATCTG GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT CT - #AACTGCTC   
 360                                                                      
- TATAATGATC GATGAAATTA TACATCACTT AAAGAGACCA CCTGCACCTT TG - #CTGGACCC   
 420                                                                      
- GAACAACCTC AATGACGAAG ACGTCTCTAT CCTGATGGAC CGAAACCTTC GA - #CTTCCAAA   
 480                                                                      
- CCTGGAGAGC TTCGTAAGGG CTGTCAAGAA CTTAGAAAAT GCATCAGGTA TT - #GAGGCAAT   
 540                                                                      
- TCTTCGTAAT CTCCAACCAT GTCTGCCCTC TGCCACGGCC GCACCCTCTC GA - #CATCCAAT   
 600                                                                      
- CATCATCAAG GCAGGTGACT GGCAAGAATT CCGGGAAAAA CTGACGTTCT AT - #CTGGTTAC   
 660                                                                      
#            688   GAAC AACAGTAC                                          
- (2) INFORMATION FOR SEQ ID NO:85:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 712 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "SYNTHETIC"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:85:                            
- CATGGCTAAC TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA GA - #CCACCTGC   
  60                                                                      
- ACCTTTGCTG GACCCGAACA ACCTCAATGA CGAAGACGTC TCTATCCTGA TG - #GACCGAAA   
 120                                                                      
- CCTTCGACTT CCAAACCTGG AGAGCTTCGT AAGGGCTGTC AAGAACTTAG AA - #AATGCATC   
 180                                                                      
- AGGTATTGAG GCAATTCTTC GTAATCTCCA ACCATGTCTG CCCTCTGCCA CG - #GCCGCACC   
 240                                                                      
- CTCTCGACAT CCAATCATCA TCAAGGCAGG TGACTGGCAA GAATTCCGGG AA - #AAACTGAC   
 300                                                                      
- GTTCTATCTG GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT CT - #GGCGGTGG   
 360                                                                      
- CAGCGGCGGC GGTTCTAACT GCTCTATAAT GATCGATGAA ATTATACATC AC - #TTAAAGAG   
 420                                                                      
- ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CT - #ATCCTGAT   
 480                                                                      
- GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AG - #AACTTAGA   
 540                                                                      
- AAATGCATCA GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CC - #TCTGCCAC   
 600                                                                      
- GGCCGCACCC TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AA - #TTCCGGGA   
 660                                                                      
- AAAACTGACG TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT AC - #           
 712                                                                      
- (2) INFORMATION FOR SEQ ID NO:86:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 975 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:86:                            
- ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
  60                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 120                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 180                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 240                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TA - #ACTGCTCT   
 300                                                                      
- ATAATGATCG ATGAAATTAT ACATCACTTA AAGAGACCAC CTGCACCTTT GT - #ACGTAGAG   
 360                                                                      
- GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CC - #CGTCTCCT   
 420                                                                      
- CCGTCTAAAG AATCTCATAA ATCTCCAAAC ATGGCTACCC AGGGTGCCAT GC - #CGGCCTTC   
 480                                                                      
- GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GC - #AGAGCTTC   
 540                                                                      
- CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CT - #CTGGCGGC   
 600                                                                      
- TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG CG - #ATGGCGCA   
 660                                                                      
- GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GC - #TGGTGCTG   
 720                                                                      
- CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CC - #AGGCCCTG   
 780                                                                      
- CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GG - #GGCTCCTG   
 840                                                                      
- CAGGCCCTGG AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GC - #AGCTGGAC   
 900                                                                      
- GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT GG - #CCCCTGCC   
 960                                                                      
#   975                                                                   
- (2) INFORMATION FOR SEQ ID NO:87:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 975 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:87:                            
- ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
  60                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 120                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 180                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 240                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TA - #ACTGCTCT   
 300                                                                      
- ATAATGATCG ATGAAATTAT ACATCACTTA AAGAGACCAC CTGCACCTTT GT - #ACGTAGAG   
 360                                                                      
- GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CC - #CGTCTCCT   
 420                                                                      
- CCGTCTAAAG AATCTCATAA ATCTCCAAAC ATGGCTACCC AGGGTGCCAT GC - #CGGCCTTC   
 480                                                                      
- GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GC - #AGAGCTTC   
 540                                                                      
- CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CT - #CTGGCGGC   
 600                                                                      
- TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG CG - #ATGGCGCA   
 660                                                                      
- GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GC - #TGGTGCTG   
 720                                                                      
- CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CC - #AGGCCCTG   
 780                                                                      
- CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GG - #GGCTCCTG   
 840                                                                      
- CAGGCCCTGG AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GC - #AGCTGGAC   
 900                                                                      
- GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT GG - #CCCCTGCC   
 960                                                                      
#   975                                                                   
- (2) INFORMATION FOR SEQ ID NO:88:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 975 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:88:                            
- ATGGCTGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA AG - #AATTCCGG   
  60                                                                      
- GAAAAACTGA CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GG - #GTGGTGGC   
 120                                                                      
- TCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
 180                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 240                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 300                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CT - #ACGTAGAG   
 360                                                                      
- GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CC - #CGTCTCCT   
 420                                                                      
- CCGTCTAAAG AATCTCATAA ATCTCCAAAC ATGGCTACCC AGGGTGCCAT GC - #CGGCCTTC   
 480                                                                      
- GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GC - #AGAGCTTC   
 540                                                                      
- CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CT - #CTGGCGGC   
 600                                                                      
- TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG CG - #ATGGCGCA   
 660                                                                      
- GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GC - #TGGTGCTG   
 720                                                                      
- CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CC - #AGGCCCTG   
 780                                                                      
- CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GG - #GGCTCCTG   
 840                                                                      
- CAGGCCCTGG AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GC - #AGCTGGAC   
 900                                                                      
- GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT GG - #CCCCTGCC   
 960                                                                      
#   975                                                                   
- (2) INFORMATION FOR SEQ ID NO:89:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 975 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:89:                            
- ATGGCTGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT GG - #TTACCCTT   
  60                                                                      
- GAGCAAGCGC AGGAACAACA GGGTGGTGGC TCTAACTGCT CTATAATGAT CG - #ATGAAATT   
 120                                                                      
- ATACATCACT TAAAGAGACC ACCTGCACCT TTGCTGGACC CGAACAACCT CA - #ATGACGAA   
 180                                                                      
- GACGTCTCTA TCCTGATGGA CCGAAACCTT CGACTTCCAA ACCTGGAGAG CT - #TCGTAAGG   
 240                                                                      
- GCTGTCAAGA ACTTAGAAAA TGCATCAGGT ATTGAGGCAA TTCTTCGTAA TC - #TCCAACCA   
 300                                                                      
- TGTCTGCCCT CTGCCACGGC CGCACCCTCT CGACATCCAA TCATCATCAA GT - #ACGTAGAG   
 360                                                                      
- GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CC - #CGTCTCCT   
 420                                                                      
- CCGTCTAAAG AATCTCATAA ATCTCCAAAC ATGGCTACCC AGGGTGCCAT GC - #CGGCCTTC   
 480                                                                      
- GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GC - #AGAGCTTC   
 540                                                                      
- CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CT - #CTGGCGGC   
 600                                                                      
- TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG CG - #ATGGCGCA   
 660                                                                      
- GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GC - #TGGTGCTG   
 720                                                                      
- CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CC - #AGGCCCTG   
 780                                                                      
- CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GG - #GGCTCCTG   
 840                                                                      
- CAGGCCCTGG AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GC - #AGCTGGAC   
 900                                                                      
- GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT GG - #CCCCTGCC   
 960                                                                      
#   975                                                                   
- (2) INFORMATION FOR SEQ ID NO:90:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 999 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:90:                            
- ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
  60                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 120                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 180                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 240                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TG - #GCGGTGGC   
 300                                                                      
- AGCGGCGGCG GTTCTAACTG CTCTATAATG ATCGATGAAA TTATACATCA CT - #TAAAGAGA   
 360                                                                      
- CCACCTGCAC CTTTGTACGT AGAGGGCGGT GGAGGCTCCC CGGGTGAACC GT - #CTGGTCCA   
 420                                                                      
- ATCTCTACTA TCAACCCGTC TCCTCCGTCT AAAGAATCTC ATAAATCTCC AA - #ACATGGCT   
 480                                                                      
- ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AG - #GGGTCCTG   
 540                                                                      
- GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CC - #ACCTTGCG   
 600                                                                      
- CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AG - #AGCAAGTG   
 660                                                                      
- AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CT - #ACAAGCTG   
 720                                                                      
- TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GG - #CTCCCCTG   
 780                                                                      
- AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CC - #ATAGCGGC   
 840                                                                      
- CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GT - #TGGGTCCC   
 900                                                                      
- ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GC - #AGCAGATG   
 960                                                                      
#   999            CCCC TGCCCTGCAG CCCTAATAA                              
- (2) INFORMATION FOR SEQ ID NO:91:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 999 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:91:                            
- ATGGCTAATG CATCAGGTAT TGAGGCAATT CTTCGTAATC TCCAACCATG TC - #TGCCCTCT   
  60                                                                      
- GCCACGGCCG CACCCTCTCG ACATCCAATC ATCATCAAGG CAGGTGACTG GC - #AAGAATTC   
 120                                                                      
- CGGGAAAAAC TGACGTTCTA TCTGGTTACC CTTGAGCAAG CGCAGGAACA AC - #AGGGTGGT   
 180                                                                      
- GGCTCTGGCG GTGGCAGCGG CGGCGGTTCT AACTGCTCTA TAATGATCGA TG - #AAATTATA   
 240                                                                      
- CATCACTTAA AGAGACCACC TGCACCTTTG CTGGACCCGA ACAACCTCAA TG - #ACGAAGAC   
 300                                                                      
- GTCTCTATCC TGATGGACCG AAACCTTCGA CTTCCAAACC TGGAGAGCTT CG - #TAAGGGCT   
 360                                                                      
- GTCAAGAACT TAGAATACGT AGAGGGCGGT GGAGGCTCCC CGGGTGAACC GT - #CTGGTCCA   
 420                                                                      
- ATCTCTACTA TCAACCCGTC TCCTCCGTCT AAAGAATCTC ATAAATCTCC AA - #ACATGGCT   
 480                                                                      
- ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AG - #GGGTCCTG   
 540                                                                      
- GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CC - #ACCTTGCG   
 600                                                                      
- CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AG - #AGCAAGTG   
 660                                                                      
- AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CT - #ACAAGCTG   
 720                                                                      
- TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GG - #CTCCCCTG   
 780                                                                      
- AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CC - #ATAGCGGC   
 840                                                                      
- CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GT - #TGGGTCCC   
 900                                                                      
- ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GC - #AGCAGATG   
 960                                                                      
#   999            CCCC TGCCCTGCAG CCCTAATAA                              
- (2) INFORMATION FOR SEQ ID NO:92:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 999 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:92:                            
- ATGGCTGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA AG - #AATTCCGG   
  60                                                                      
- GAAAAACTGA CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GG - #GTGGTGGC   
 120                                                                      
- TCTGGCGGTG GCAGCGGCGG CGGTTCTAAC TGCTCTATAA TGATCGATGA AA - #TTATACAT   
 180                                                                      
- CACTTAAAGA GACCACCTGC ACCTTTGCTG GACCCGAACA ACCTCAATGA CG - #AAGACGTC   
 240                                                                      
- TCTATCCTGA TGGACCGAAA CCTTCGACTT CCAAACCTGG AGAGCTTCGT AA - #GGGCTGTC   
 300                                                                      
- AAGAACTTAG AAAATGCATC AGGTATTGAG GCAATTCTTC GTAATCTCCA AC - #CATGTCTG   
 360                                                                      
- CCCTCTGCCA CGGCCTACGT AGAGGGCGGT GGAGGCTCCC CGGGTGAACC GT - #CTGGTCCA   
 420                                                                      
- ATCTCTACTA TCAACCCGTC TCCTCCGTCT AAAGAATCTC ATAAATCTCC AA - #ACATGGCT   
 480                                                                      
- ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AG - #GGGTCCTG   
 540                                                                      
- GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CC - #ACCTTGCG   
 600                                                                      
- CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AG - #AGCAAGTG   
 660                                                                      
- AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CT - #ACAAGCTG   
 720                                                                      
- TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GG - #CTCCCCTG   
 780                                                                      
- AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CC - #ATAGCGGC   
 840                                                                      
- CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GT - #TGGGTCCC   
 900                                                                      
- ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GC - #AGCAGATG   
 960                                                                      
#   999            CCCC TGCCCTGCAG CCCTAATAA                              
- (2) INFORMATION FOR SEQ ID NO:93:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 999 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:93:                            
- ATGGCTGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT GG - #TTACCCTT   
  60                                                                      
- GAGCAAGCGC AGGAACAACA GGGTGGTGGC TCTGGCGGTG GCAGCGGCGG CG - #GTTCTAAC   
 120                                                                      
- TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA GACCACCTGC AC - #CTTTGCTG   
 180                                                                      
- GACCCGAACA ACCTCAATGA CGAAGACGTC TCTATCCTGA TGGACCGAAA CC - #TTCGACTT   
 240                                                                      
- CCAAACCTGG AGAGCTTCGT AAGGGCTGTC AAGAACTTAG AAAATGCATC AG - #GTATTGAG   
 300                                                                      
- GCAATTCTTC GTAATCTCCA ACCATGTCTG CCCTCTGCCA CGGCCGCACC CT - #CTCGACAT   
 360                                                                      
- CCAATCATCA TCAAGTACGT AGAGGGCGGT GGAGGCTCCC CGGGTGAACC GT - #CTGGTCCA   
 420                                                                      
- ATCTCTACTA TCAACCCGTC TCCTCCGTCT AAAGAATCTC ATAAATCTCC AA - #ACATGGCT   
 480                                                                      
- ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AG - #GGGTCCTG   
 540                                                                      
- GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CC - #ACCTTGCG   
 600                                                                      
- CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AG - #AGCAAGTG   
 660                                                                      
- AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CT - #ACAAGCTG   
 720                                                                      
- TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GG - #CTCCCCTG   
 780                                                                      
- AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CC - #ATAGCGGC   
 840                                                                      
- CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GT - #TGGGTCCC   
 900                                                                      
- ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GC - #AGCAGATG   
 960                                                                      
#   999            CCCC TGCCCTGCAG CCCTAATAA                              
- (2) INFORMATION FOR SEQ ID NO:94:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 918 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:94:                            
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT ACAAGCTGTG CC - #ACCCCGAG   
 420                                                                      
- GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG CTCCCCTGAG CT - #CCTGCCCC   
 480                                                                      
- AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TT - #TCCTCTAC   
 540                                                                      
- CAGGGGCTCC TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CT - #TGGACACA   
 600                                                                      
- CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AG - #AACTGGGA   
 660                                                                      
- ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG CCTTCGCCTC TG - #CTTTCCAG   
 720                                                                      
- CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC CATCTGCAGA GCTTCCTGGA GG - #TGTCGTAC   
 780                                                                      
- CGCGTTCTAC GCCACCTTGC GCAGCCCTCT GGCGGCTCTG GCGGCTCTCA GA - #GCTTCCTG   
 840                                                                      
- CTCAAGTCTT TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CC - #AGGAGAAG   
 900                                                                      
# 918              AA                                                     
- (2) INFORMATION FOR SEQ ID NO:95:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 963 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:95:                            
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTTACAAG CTGTGCCACC CCGAGGAGCT GG - #TGCTGCTC   
 480                                                                      
- GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GG - #CCCTGCAG   
 540                                                                      
- CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GC - #TCCTGCAG   
 600                                                                      
- GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GC - #TGGACGTC   
 660                                                                      
- GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CC - #CTGCCCTG   
 720                                                                      
- CAGCCCACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GG - #CAGGAGGG   
 780                                                                      
- GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TC - #TACGCCAC   
 840                                                                      
- CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC TCTCAGAGCT TCCTGCTCAA GT - #CTTTAGAG   
 900                                                                      
- CAAGTGAGAA AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TG - #CCACCTAA   
 960                                                                      
#            963                                                          
- (2) INFORMATION FOR SEQ ID NO:96:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 918 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:96:                            
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTC CCGAGTTGGG TC - #CCACCTTG   
 420                                                                      
- GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA GA - #TGGAAGAA   
 480                                                                      
- CTGGGAATGG CCCCTGCCCT GCAGCCCACC CAGGGTGCCA TGCCGGCCTT CG - #CCTCTGCT   
 540                                                                      
- TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT CC - #TGGAGGTG   
 600                                                                      
- TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCTCTGGCG GCTCTGGCGG CT - #CTCAGAGC   
 660                                                                      
- TTCCTGCTCA AGTCTTTAGA GCAAGTGAGA AAGATCCAGG GCGATGGCGC AG - #CGCTCCAG   
 720                                                                      
- GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GC - #TCGGACAC   
 780                                                                      
- TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GC - #AGCTGGCA   
 840                                                                      
- GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GC - #AGGCCCTG   
 900                                                                      
# 918              AA                                                     
- (2) INFORMATION FOR SEQ ID NO:97:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 963 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:97:                            
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTCCCGAG TTGGGTCCCA CCTTGGACAC AC - #TGCAGCTG   
 480                                                                      
- GACGTCGCCG ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AA - #TGGCCCCT   
 540                                                                      
- GCCCTGCAGC CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GC - #GCCGGGCA   
 600                                                                      
- GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CC - #GCGTTCTA   
 660                                                                      
- CGCCACCTTG CGCAGCCCTC TGGCGGCTCT GGCGGCTCTC AGAGCTTCCT GC - #TCAAGTCT   
 720                                                                      
- TTAGAGCAAG TGAGAAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA GC - #TGTGTGCC   
 780                                                                      
- ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG GACACTCTCT GG - #GCATCCCC   
 840                                                                      
- TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CT - #TGAGCCAA   
 900                                                                      
- CTCCATAGCG GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GA - #TATCCTAA   
 960                                                                      
#            963                                                          
- (2) INFORMATION FOR SEQ ID NO:98:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 918 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:98:                            
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA TGGCCCCTGC CC - #TGCAGCCC   
 420                                                                      
- ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AG - #GGGTCCTG   
 480                                                                      
- GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CC - #ACCTTGCG   
 540                                                                      
- CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AG - #AGCAAGTG   
 600                                                                      
- AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CT - #ACAAGCTG   
 660                                                                      
- TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GG - #CTCCCCTG   
 720                                                                      
- AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CC - #ATAGCGGC   
 780                                                                      
- CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GT - #TGGGTCCC   
 840                                                                      
- ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GC - #AGCAGATG   
 900                                                                      
# 918              AA                                                     
- (2) INFORMATION FOR SEQ ID NO:99:                                       
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 963 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:99:                            
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTATGGCC CCTGCCCTGC AGCCCACCCA GG - #GTGCCATG   
 480                                                                      
- CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TA - #GCCATCTG   
 540                                                                      
- CAGAGCTTCC TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CT - #CTGGCGGC   
 600                                                                      
- TCTGGCGGCT CTCAGAGCTT CCTGCTCAAG TCTTTAGAGC AAGTGAGAAA GA - #TCCAGGGC   
 660                                                                      
- GATGGCGCAG CGCTCCAGGA GAAGCTGTGT GCCACCTACA AGCTGTGCCA CC - #CCGAGGAG   
 720                                                                      
- CTGGTGCTGC TCGGACACTC TCTGGGCATC CCCTGGGCTC CCCTGAGCTC CT - #GCCCCAGC   
 780                                                                      
- CAGGCCCTGC AGCTGGCAGG CTGCTTGAGC CAACTCCATA GCGGCCTTTT CC - #TCTACCAG   
 840                                                                      
- GGGCTCCTGC AGGCCCTGGA AGGGATATCC CCCGAGTTGG GTCCCACCTT GG - #ACACACTG   
 900                                                                      
- CAGCTGGACG TCGCCGACTT TGCCACCACC ATCTGGCAGC AGATGGAAGA AC - #TGGGATAA   
 960                                                                      
#            963                                                          
- (2) INFORMATION FOR SEQ ID NO:100:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 918 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:100:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA CCCAGGGTGC CA - #TGCCGGCC   
 420                                                                      
- TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA GGGGTCCTGG TTGCTAGCCA TC - #TGCAGAGC   
 480                                                                      
- TTCCTGGAGG TGTCGTACCG CGTTCTACGC CACCTTGCGC AGCCCTCTGG CG - #GCTCTGGC   
 540                                                                      
- GGCTCTCAGA GCTTCCTGCT CAAGTCTTTA GAGCAAGTGA GAAAGATCCA GG - #GCGATGGC   
 600                                                                      
- GCAGCGCTCC AGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GG - #AGCTGGTG   
 660                                                                      
- CTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCC CA - #GCCAGGCC   
 720                                                                      
- CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCC TTTTCCTCTA CC - #AGGGGCTC   
 780                                                                      
- CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG TTGGGTCCCA CCTTGGACAC AC - #TGCAGCTG   
 840                                                                      
- GACGTCGCCG ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AA - #TGGCCCCT   
 900                                                                      
# 918              AA                                                     
- (2) INFORMATION FOR SEQ ID NO:101:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 963 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:101:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CT - #CTGCTTTC   
 480                                                                      
- CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GG - #AGGTGTCG   
 540                                                                      
- TACCGCGTTC TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TC - #AGAGCTTC   
 600                                                                      
- CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC GC - #TCCAGGAG   
 660                                                                      
- AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CG - #GACACTCT   
 720                                                                      
- CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA GC - #TGGCAGGC   
 780                                                                      
- TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GG - #CCCTGGAA   
 840                                                                      
- GGGATATCCC CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CG - #CCGACTTT   
 900                                                                      
- GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT GC - #AGCCCTAA   
 960                                                                      
#            963                                                          
- (2) INFORMATION FOR SEQ ID NO:102:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 918 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:102:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT CTGCTTTCCA GC - #GCCGGGCA   
 420                                                                      
- GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CC - #GCGTTCTA   
 480                                                                      
- CGCCACCTTG CGCAGCCCTC TGGCGGCTCT GGCGGCTCTC AGAGCTTCCT GC - #TCAAGTCT   
 540                                                                      
- TTAGAGCAAG TGAGAAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA GC - #TGTGTGCC   
 600                                                                      
- ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG GACACTCTCT GG - #GCATCCCC   
 660                                                                      
- TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CT - #TGAGCCAA   
 720                                                                      
- CTCCATAGCG GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GA - #TATCCCCC   
 780                                                                      
- GAGTTGGGTC CCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CA - #CCACCATC   
 840                                                                      
- TGGCAGCAGA TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCA GG - #GTGCCATG   
 900                                                                      
# 918              AA                                                     
- (2) INFORMATION FOR SEQ ID NO:103:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 963 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "SYNTHETIC"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:103:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTTCTGCT TTCCAGCGCC GGGCAGGAGG GG - #TCCTGGTT   
 480                                                                      
- GCTAGCCATC TGCAGAGCTT CCTGGAGGTG TCGTACCGCG TTCTACGCCA CC - #TTGCGCAG   
 540                                                                      
- CCCTCTGGCG GCTCTGGCGG CTCTCAGAGC TTCCTGCTCA AGTCTTTAGA GC - #AAGTGAGA   
 600                                                                      
- AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CA - #AGCTGTGC   
 660                                                                      
- CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC TC - #CCCTGAGC   
 720                                                                      
- TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA GCCAACTCCA TA - #GCGGCCTT   
 780                                                                      
- TTCCTCTACC AGGGGCTCCT GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GG - #GTCCCACC   
 840                                                                      
- TTGGACACAC TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCA GC - #AGATGGAA   
 900                                                                      
- GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CT - #TCGCCTAA   
 960                                                                      
#            963                                                          
- (2) INFORMATION FOR SEQ ID NO:104:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:104:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT ACAAGCTGTG CC - #ACCCCGAG   
 420                                                                      
- GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG CTCCCCTGAG CT - #CCTGCCCC   
 480                                                                      
- AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TT - #TCCTCTAC   
 540                                                                      
- CAGGGGCTCC TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CT - #TGGACACA   
 600                                                                      
- CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AG - #AACTGGGA   
 660                                                                      
- ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG CCTTCGCCTC TG - #CTTTCCAG   
 720                                                                      
- CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC CATCTGCAGA GCTTCCTGGA GG - #TGTCGTAC   
 780                                                                      
- CGCGTTCTAC GCCACCTTGC GCAGCCCACA CCATTGGGCC CTGCCAGCTC CC - #TGCCCCAG   
 840                                                                      
- AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG AGAAAGATCC AGGGCGATGG CG - #CAGCGCTC   
 900                                                                      
#            927   CCAC CTAATAA                                           
- (2) INFORMATION FOR SEQ ID NO:105:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 972 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:105:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTTACAAG CTGTGCCACC CCGAGGAGCT GG - #TGCTGCTC   
 480                                                                      
- GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GG - #CCCTGCAG   
 540                                                                      
- CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GC - #TCCTGCAG   
 600                                                                      
- GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GC - #TGGACGTC   
 660                                                                      
- GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CC - #CTGCCCTG   
 720                                                                      
- CAGCCCACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GG - #CAGGAGGG   
 780                                                                      
- GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TC - #TACGCCAC   
 840                                                                      
- CTTGCGCAGC CCACACCATT GGGCCCTGCC AGCTCCCTGC CCCAGAGCTT CC - #TGCTCAAG   
 900                                                                      
- TCTTTAGAGC AAGTGAGAAA GATCCAGGGC GATGGCGCAG CGCTCCAGGA GA - #AGCTGTGT   
 960                                                                      
#      972                                                                
- (2) INFORMATION FOR SEQ ID NO:106:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:106:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTC CCGAGTTGGG TC - #CCACCTTG   
 420                                                                      
- GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA GA - #TGGAAGAA   
 480                                                                      
- CTGGGAATGG CCCCTGCCCT GCAGCCCACC CAGGGTGCCA TGCCGGCCTT CG - #CCTCTGCT   
 540                                                                      
- TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT CC - #TGGAGGTG   
 600                                                                      
- TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCACACCAT TGGGCCCTGC CA - #GCTCCCTG   
 660                                                                      
- CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG CG - #ATGGCGCA   
 720                                                                      
- GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GC - #TGGTGCTG   
 780                                                                      
- CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CC - #AGGCCCTG   
 840                                                                      
- CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GG - #GGCTCCTG   
 900                                                                      
#            927   TATC CTAATAA                                           
- (2) INFORMATION FOR SEQ ID NO:107:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 972 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:107:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTCCCGAG TTGGGTCCCA CCTTGGACAC AC - #TGCAGCTG   
 480                                                                      
- GACGTCGCCG ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AA - #TGGCCCCT   
 540                                                                      
- GCCCTGCAGC CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GC - #GCCGGGCA   
 600                                                                      
- GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CC - #GCGTTCTA   
 660                                                                      
- CGCCACCTTG CGCAGCCCAC ACCATTGGGC CCTGCCAGCT CCCTGCCCCA GA - #GCTTCCTG   
 720                                                                      
- CTCAAGTCTT TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CC - #AGGAGAAG   
 780                                                                      
- CTGTGTGCCA CCTACAAGCT GTGCCACCCC GAGGAGCTGG TGCTGCTCGG AC - #ACTCTCTG   
 840                                                                      
- GGCATCCCCT GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG CCCTGCAGCT GG - #CAGGCTGC   
 900                                                                      
- TTGAGCCAAC TCCATAGCGG CCTTTTCCTC TACCAGGGGC TCCTGCAGGC CC - #TGGAAGGG   
 960                                                                      
#      972                                                                
- (2) INFORMATION FOR SEQ ID NO:108:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:108:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA TGGCCCCTGC CC - #TGCAGCCC   
 420                                                                      
- ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AG - #GGGTCCTG   
 480                                                                      
- GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CC - #ACCTTGCG   
 540                                                                      
- CAGCCCACAC CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CA - #AGTCTTTA   
 600                                                                      
- GAGCAAGTGA GAAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GT - #GTGCCACC   
 660                                                                      
- TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CA - #TCCCCTGG   
 720                                                                      
- GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GA - #GCCAACTC   
 780                                                                      
- CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT AT - #CCCCCGAG   
 840                                                                      
- TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CA - #CCATCTGG   
 900                                                                      
#            927   TGGG ATAATAA                                           
- (2) INFORMATION FOR SEQ ID NO:109:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 972 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "DNA (synthetic)"PTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:109:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTATGGCC CCTGCCCTGC AGCCCACCCA GG - #GTGCCATG   
 480                                                                      
- CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TA - #GCCATCTG   
 540                                                                      
- CAGAGCTTCC TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CA - #CACCATTG   
 600                                                                      
- GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA AG - #TGAGAAAG   
 660                                                                      
- ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG CCACCTACAA GC - #TGTGCCAC   
 720                                                                      
- CCCGAGGAGC TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CC - #TGAGCTCC   
 780                                                                      
- TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG CG - #GCCTTTTC   
 840                                                                      
- CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TC - #CCACCTTG   
 900                                                                      
- GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA GA - #TGGAAGAA   
 960                                                                      
#      972                                                                
- (2) INFORMATION FOR SEQ ID NO:110:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:110:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA CCCAGGGTGC CA - #TGCCGGCC   
 420                                                                      
- TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA GGGGTCCTGG TTGCTAGCCA TC - #TGCAGAGC   
 480                                                                      
- TTCCTGGAGG TGTCGTACCG CGTTCTACGC CACCTTGCGC AGCCCACACC AT - #TGGGCCCT   
 540                                                                      
- GCCAGCTCCC TGCCCCAGAG CTTCCTGCTC AAGTCTTTAG AGCAAGTGAG AA - #AGATCCAG   
 600                                                                      
- GGCGATGGCG CAGCGCTCCA GGAGAAGCTG TGTGCCACCT ACAAGCTGTG CC - #ACCCCGAG   
 660                                                                      
- GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG CTCCCCTGAG CT - #CCTGCCCC   
 720                                                                      
- AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TT - #TCCTCTAC   
 780                                                                      
- CAGGGGCTCC TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CT - #TGGACACA   
 840                                                                      
- CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AG - #AACTGGGA   
 900                                                                      
#            927   AGCC CTAATAA                                           
- (2) INFORMATION FOR SEQ ID NO:111:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 972 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:111:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CT - #CTGCTTTC   
 480                                                                      
- CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GG - #AGGTGTCG   
 540                                                                      
- TACCGCGTTC TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CT - #CCCTGCCC   
 600                                                                      
- CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA TG - #GCGCAGCG   
 660                                                                      
- CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC CCGAGGAGCT GG - #TGCTGCTC   
 720                                                                      
- GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GG - #CCCTGCAG   
 780                                                                      
- CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GC - #TCCTGCAG   
 840                                                                      
- GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GC - #TGGACGTC   
 900                                                                      
- GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CC - #CTGCCCTG   
 960                                                                      
#      972                                                                
- (2) INFORMATION FOR SEQ ID NO:112:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:112:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT CTGCTTTCCA GC - #GCCGGGCA   
 420                                                                      
- GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CC - #GCGTTCTA   
 480                                                                      
- CGCCACCTTG CGCAGCCCAC ACCATTGGGC CCTGCCAGCT CCCTGCCCCA GA - #GCTTCCTG   
 540                                                                      
- CTCAAGTCTT TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CC - #AGGAGAAG   
 600                                                                      
- CTGTGTGCCA CCTACAAGCT GTGCCACCCC GAGGAGCTGG TGCTGCTCGG AC - #ACTCTCTG   
 660                                                                      
- GGCATCCCCT GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG CCCTGCAGCT GG - #CAGGCTGC   
 720                                                                      
- TTGAGCCAAC TCCATAGCGG CCTTTTCCTC TACCAGGGGC TCCTGCAGGC CC - #TGGAAGGG   
 780                                                                      
- ATATCCCCCG AGTTGGGTCC CACCTTGGAC ACACTGCAGC TGGACGTCGC CG - #ACTTTGCC   
 840                                                                      
- ACCACCATCT GGCAGCAGAT GGAAGAACTG GGAATGGCCC CTGCCCTGCA GC - #CCACCCAG   
 900                                                                      
#            927   TCGC CTAATAA                                           
- (2) INFORMATION FOR SEQ ID NO:113:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 972 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:113:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ACCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTTCTGCT TTCCAGCGCC GGGCAGGAGG GG - #TCCTGGTT   
 480                                                                      
- GCTAGCCATC TGCAGAGCTT CCTGGAGGTG TCGTACCGCG TTCTACGCCA CC - #TTGCGCAG   
 540                                                                      
- CCCACACCAT TGGGCCCTGC CAGCTCCCTG CCCCAGAGCT TCCTGCTCAA GT - #CTTTAGAG   
 600                                                                      
- CAAGTGAGAA AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TG - #CCACCTAC   
 660                                                                      
- AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CC - #CCTGGGCT   
 720                                                                      
- CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG CC - #AACTCCAT   
 780                                                                      
- AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG AAGGGATATC CC - #CCGAGTTG   
 840                                                                      
- GGTCCCACCT TGGACACACT GCAGCTGGAC GTCGCCGACT TTGCCACCAC CA - #TCTGGCAG   
 900                                                                      
- CAGATGGAAG AACTGGGAAT GGCCCCTGCC CTGCAGCCCA CCCAGGGTGC CA - #TGCCGGCC   
 960                                                                      
#      972                                                                
- (2) INFORMATION FOR SEQ ID NO:114:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 963 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:114:                           
- ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GC - #CACCGCTG   
  60                                                                      
- CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTAAT GG - #ACAATAAC   
 120                                                                      
- CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GA - #ATGCATCA   
 180                                                                      
- GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CGCTAGCCAC GG - #CCGCACCC   
 240                                                                      
- ACGCGACATC CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TA - #AACTGACC   
 300                                                                      
- TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CT - #CTGCTTTC   
 480                                                                      
- CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GG - #AGGTGTCG   
 540                                                                      
- TACCGCGTTC TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TC - #AGAGCTTC   
 600                                                                      
- CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC GC - #TCCAGGAG   
 660                                                                      
- AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CG - #GACACTCT   
 720                                                                      
- CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA GC - #TGGCAGGC   
 780                                                                      
- TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GG - #CCCTGGAA   
 840                                                                      
- GGGATATCCC CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CG - #CCGACTTT   
 900                                                                      
- GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT GC - #AGCCCTAA   
 960                                                                      
#            963                                                          
- (2) INFORMATION FOR SEQ ID NO:115:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 972 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:115:                           
- ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GC - #CACCGCTG   
  60                                                                      
- CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTGAT GG - #AAAATAAC   
 120                                                                      
- CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GA - #ATGCATCA   
 180                                                                      
- GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CCCTGGCCAC GG - #CCGCACCC   
 240                                                                      
- ACGCGACATC CAATCATCAT CCGTGACGGT GACTGGAATG AATTCCGTCG TA - #AACTGACC   
 300                                                                      
- TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CT - #CTGCTTTC   
 480                                                                      
- CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GG - #AGGTGTCG   
 540                                                                      
- TACCGCGTTC TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CT - #CCCTGCCC   
 600                                                                      
- CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA TG - #GCGCAGCG   
 660                                                                      
- CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC CCGAGGAGCT GG - #TGCTGCTC   
 720                                                                      
- GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GG - #CCCTGCAG   
 780                                                                      
- CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GC - #TCCTGCAG   
 840                                                                      
- GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GC - #TGGACGTC   
 900                                                                      
- GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CC - #CTGCCCTG   
 960                                                                      
#      972                                                                
- (2) INFORMATION FOR SEQ ID NO:116:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 963 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:116:                           
- ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GC - #CACCGCTG   
  60                                                                      
- CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTGAT GG - #AAAATAAC   
 120                                                                      
- CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GA - #ATGCATCA   
 180                                                                      
- GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CCCTGGCCAC GG - #CCGCACCC   
 240                                                                      
- ACGCGACATC CAATCATCAT CCGTGACGGT GACTGGAATG AATTCCGTCG TA - #AACTGACC   
 300                                                                      
- TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CT - #CTGCTTTC   
 480                                                                      
- CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GG - #AGGTGTCG   
 540                                                                      
- TACCGCGTTC TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TC - #AGAGCTTC   
 600                                                                      
- CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC GC - #TCCAGGAG   
 660                                                                      
- AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CG - #GACACTCT   
 720                                                                      
- CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA GC - #TGGCAGGC   
 780                                                                      
- TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GG - #CCCTGGAA   
 840                                                                      
- GGGATATCCC CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CG - #CCGACTTT   
 900                                                                      
- GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT GC - #AGCCCTAA   
 960                                                                      
#            963                                                          
- (2) INFORMATION FOR SEQ ID NO:117:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 972 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:117:                           
- ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GC - #CACCGCTG   
  60                                                                      
- CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTAAT GG - #ACAATAAC   
 120                                                                      
- CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GA - #ATGCATCA   
 180                                                                      
- GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CGCTAGCCAC GG - #CCGCACCC   
 240                                                                      
- ACGCGACATC CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TA - #AACTGACC   
 300                                                                      
- TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CT - #CTGCTTTC   
 480                                                                      
- CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GG - #AGGTGTCG   
 540                                                                      
- TACCGCGTTC TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CT - #CCCTGCCC   
 600                                                                      
- CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA TG - #GCGCAGCG   
 660                                                                      
- CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC CCGAGGAGCT GG - #TGCTGCTC   
 720                                                                      
- GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GG - #CCCTGCAG   
 780                                                                      
- CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GC - #TCCTGCAG   
 840                                                                      
- GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GC - #TGGACGTC   
 900                                                                      
- GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CC - #CTGCCCTG   
 960                                                                      
#      972                                                                
- (2) INFORMATION FOR SEQ ID NO:118:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 918 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:118:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGA GGTTCACCCT TTGCCTACAC CTGTCCTGCT GC - #CTGCTGTG   
 480                                                                      
- GACTTTAGCT TGGGAGAATG GAAAACCCAG ATGGAGGAGA CCAAGGCACA GG - #ACATTCTG   
 540                                                                      
- GGAGCAGTGA CCCTTCTGCT GGAGGGAGTG ATGGCAGCAC GGGGACAACT GG - #GACCCACT   
 600                                                                      
- TGCCTCTCAT CCCTCCTGGG GCAGCTTTCT GGACAGGTCC GTCTCCTCCT TG - #GGGCCCTG   
 660                                                                      
- CAGAGCCTCC TTGGAACCCA GCTTCCTCCA CAGGGCAGGA CCACAGCTCA CA - #AGGATCCC   
 720                                                                      
- AATGCCATCT TCCTGAGCTT CCAACACCTG CTCCGAGGAA AGGTGCGTTT CC - #TGATGCTT   
 780                                                                      
- GTAGGAGGGT CCACCCTCTG CGTCAGGGAA TTCGGCGGCA ACATGGCGTC TC - #CCGCTCCG   
 840                                                                      
- CCTGCTTGTG ACCTCCGAGT CCTCAGTAAA CTGCTTCGTG ACTCCCATGT CC - #TTCACAGC   
 900                                                                      
# 918              CA                                                     
- (2) INFORMATION FOR SEQ ID NO:119:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 918 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:119:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGTT GCCTACACCT GTCCTGCTGC CTGCTGTGGA CT - #TTAGCTTG   
 480                                                                      
- GGAGAATGGA AAACCCAGAT GGAGGAGACC AAGGCACAGG ACATTCTGGG AG - #CAGTGACC   
 540                                                                      
- CTTCTGCTGG AGGGAGTGAT GGCAGCACGG GGACAACTGG GACCCACTTG CC - #TCTCATCC   
 600                                                                      
- CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT CTCCTCCTTG GGGCCCTGCA GA - #GCCTCCTT   
 660                                                                      
- GGAACCCAGC TTCCTCCACA GGGCAGGACC ACAGCTCACA AGGATCCCAA TG - #CCATCTTC   
 720                                                                      
- CTGAGCTTCC AACACCTGCT CCGAGGAAAG GTGCGTTTCC TGATGCTTGT AG - #GAGGGTCC   
 780                                                                      
- ACCCTCTGCG TCAGGGAATT CGGCGGCAAC ATGGCGTCTC CCGCTCCGCC TG - #CTTGTGAC   
 840                                                                      
- CTCCGAGTCC TCAGTAAACT GCTTCGTGAC TCCCATGTCC TTCACAGCAG AC - #TGAGCCAG   
 900                                                                      
# 918              CT                                                     
- (2) INFORMATION FOR SEQ ID NO:120:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 918 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:120:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGT CCTGCTGCCT GCTGTGGACT TTAGCTTGGG AG - #AATGGAAA   
 480                                                                      
- ACCCAGATGG AGGAGACCAA GGCACAGGAC ATTCTGGGAG CAGTGACCCT TC - #TGCTGGAG   
 540                                                                      
- GGAGTGATGG CAGCACGGGG ACAACTGGGA CCCACTTGCC TCTCATCCCT CC - #TGGGGCAG   
 600                                                                      
- CTTTCTGGAC AGGTCCGTCT CCTCCTTGGG GCCCTGCAGA GCCTCCTTGG AA - #CCCAGCTT   
 660                                                                      
- CCTCCACAGG GCAGGACCAC AGCTCACAAG GATCCCAATG CCATCTTCCT GA - #GCTTCCAA   
 720                                                                      
- CACCTGCTCC GAGGAAAGGT GCGTTTCCTG ATGCTTGTAG GAGGGTCCAC CC - #TCTGCGTC   
 780                                                                      
- AGGGAATTCG GCGGCAACAT GGCGTCTCCC GCTCCGCCTG CTTGTGACCT CC - #GAGTCCTC   
 840                                                                      
- AGTAAACTGC TTCGTGACTC CCATGTCCTT CACAGCAGAC TGAGCCAGTG CC - #CAGAGGTT   
 900                                                                      
# 918              CT                                                     
- (2) INFORMATION FOR SEQ ID NO:121:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 918 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:121:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CC - #AGATGGAG   
 480                                                                      
- GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AG - #TGATGGCA   
 540                                                                      
- GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TT - #CTGGACAG   
 600                                                                      
- GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGCTTCC TC - #CACAGGGC   
 660                                                                      
- AGGACCACAG CTCACAAGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CC - #TGCTCCGA   
 720                                                                      
- GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GG - #AATTCGGC   
 780                                                                      
- GGCAACATGG CGTCTCCCGC TCCGCCTGCT TGTGACCTCC GAGTCCTCAG TA - #AACTGCTT   
 840                                                                      
- CGTGACTCCC ATGTCCTTCA CAGCAGACTG AGCCAGTGCC CAGAGGTTCA CC - #CTTTGCCT   
 900                                                                      
# 918              CT                                                     
- (2) INFORMATION FOR SEQ ID NO:122:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 918 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:122:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGA CTTTAGCTTG GGAGAATGGA AAACCCAGAT GG - #AGGAGACC   
 480                                                                      
- AAGGCACAGG ACATTCTGGG AGCAGTGACC CTTCTGCTGG AGGGAGTGAT GG - #CAGCACGG   
 540                                                                      
- GGACAACTGG GACCCACTTG CCTCTCATCC CTCCTGGGGC AGCTTTCTGG AC - #AGGTCCGT   
 600                                                                      
- CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT GGAACCCAGC TTCCTCCACA GG - #GCAGGACC   
 660                                                                      
- ACAGCTCACA AGGATCCCAA TGCCATCTTC CTGAGCTTCC AACACCTGCT CC - #GAGGAAAG   
 720                                                                      
- GTGCGTTTCC TGATGCTTGT AGGAGGGTCC ACCCTCTGCG TCAGGGAATT CG - #GCGGCAAC   
 780                                                                      
- ATGGCGTCTC CCGCTCCGCC TGCTTGTGAC CTCCGAGTCC TCAGTAAACT GC - #TTCGTGAC   
 840                                                                      
- TCCCATGTCC TTCACAGCAG ACTGAGCCAG TGCCCAGAGG TTCACCCTTT GC - #CTACACCT   
 900                                                                      
# 918              TG                                                     
- (2) INFORMATION FOR SEQ ID NO:123:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 907 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:123:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCGGTTAC CCTTGAGCAA GCGCAGGAAC AACAGTACGT AGAGGGCGGT GG - #AGGCTCCC   
 360                                                                      
- CGGGGAACCG TCTGGTCCAA TCTCTACTAT CAACCCGTCT CCTCCGTCTA AA - #GAATCTCA   
 420                                                                      
- TAAACTCCAA ACATGGGAGA ATGGAAAACC CAGATGGAGG AGACCAAGGC AC - #AGGACATT   
 480                                                                      
- CTGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA CT - #GGGACCCA   
 540                                                                      
- CTTGCTCTCA TCCCTCCTGG GGCAGCTTTC TGGACAGGTC CGTCTCCTCC TT - #GGGGCCCT   
 600                                                                      
- GCAGGCCTCC TTGGAACCCA GCTTCCTCCA CAGGGCAGGA CCACAGCTCA CA - #AGGATCCC   
 660                                                                      
- AATGCATCTT CCTGAGCTTC CAACACCTGC TCCGAGGAAA GGTGCGTTTC CT - #GATGCTTG   
 720                                                                      
- TAGGGGGTCC ACCCTCTGCG TCAGGGAATT CGGCGGCAAC ATGGCGTCTC CC - #GCTCCGCC   
 780                                                                      
- TGCTGTGACC TCCGAGTCCT CAGTAAACTG CTTCGTGACT CCCATGTCCT TC - #ACAGCAGA   
 840                                                                      
- CTGACCAGTG CCCAGAGGTT CACCCTTTGC CTACACCTGT CCTGCTGCCT GC - #TGTGGACT   
 900                                                                      
#         907                                                             
- (2) INFORMATION FOR SEQ ID NO:124:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 918 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:124:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGG ACCCACTTGC CTCTCATCCC TCCTGGGGCA GC - #TTTCTGGA   
 480                                                                      
- CAGGTCCGTC TCCTCCTTGG GGCCCTGCAG AGCCTCCTTG GAACCCAGCT TC - #CTCCACAG   
 540                                                                      
- GGCAGGACCA CAGCTCACAA GGATCCCAAT GCCATCTTCC TGAGCTTCCA AC - #ACCTGCTC   
 600                                                                      
- CGAGGAAAGG TGCGTTTCCT GATGCTTGTA GGAGGGTCCA CCCTCTGCGT CA - #GGGAATTC   
 660                                                                      
- GGCGGCAACA TGGCGTCTCC CGCTCCGCCT GCTTGTGACC TCCGAGTCCT CA - #GTAAACTG   
 720                                                                      
- CTTCGTGACT CCCATGTCCT TCACAGCAGA CTGAGCCAGT GCCCAGAGGT TC - #ACCCTTTG   
 780                                                                      
- CCTACACCTG TCCTGCTGCC TGCTGTGGAC TTTAGCTTGG GAGAATGGAA AA - #CCCAGATG   
 840                                                                      
- GAGGAGACCA AGGCACAGGA CATTCTGGGA GCAGTGACCC TTCTGCTGGA GG - #GAGTGATG   
 900                                                                      
# 918              TG                                                     
- (2) INFORMATION FOR SEQ ID NO:125:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 848 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:125:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGG AACCCAGCTT CCTCCACAGG GCAGGACCAC AG - #CTCACAAG   
 480                                                                      
- GATCCCAATG CCATCTTCCT GAGCTTCCAA CACCTGCTCC GAGGAAAGGT GC - #GTTTCCTG   
 540                                                                      
- ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC AGGGAATTCG GCGGCAACAT GG - #CGTCTCCC   
 600                                                                      
- GCTCCGCCTG CTTGTGACCT CCGAGTCCTC AGTAAACTGC TTCGTGACTC CC - #ATGTCCTT   
 660                                                                      
- CACAGCAGAC TGAGCCAGTG CCCAGAGGTT CACCCTTTGC CTACACCTGT CC - #TGCTGCCT   
 720                                                                      
- GCTGTGGACT TTAGCTTGGG AGAATGGAAA ACCCAGATGG AGGAGACCAA GG - #CACAGGAC   
 780                                                                      
- ATTCTGGGAG CAGTGACCCT TCTGCTGGAG GGAGTGATGG CAGCACGGGG AC - #AACTGGGA   
 840                                                                      
#         848                                                             
- (2) INFORMATION FOR SEQ ID NO:126:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 918 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:126:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGG CAGGACCACA GCTCACAAGG ATCCCAATGC CA - #TCTTCCTG   
 480                                                                      
- AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG CGTTTCCTGA TGCTTGTAGG AG - #GGTCCACC   
 540                                                                      
- CTCTGCGTCA GGGAATTCGG CGGCAACATG GCGTCTCCCG CTCCGCCTGC TT - #GTGACCTC   
 600                                                                      
- CGAGTCCTCA GTAAACTGCT TCGTGACTCC CATGTCCTTC ACAGCAGACT GA - #GCCAGTGC   
 660                                                                      
- CCAGAGGTTC ACCCTTTGCC TACACCTGTC CTGCTGCCTG CTGTGGACTT TA - #GCTTGGGA   
 720                                                                      
- GAATGGAAAA CCCAGATGGA GGAGACCAAG GCACAGGACA TTCTGGGAGC AG - #TGACCCTT   
 780                                                                      
- CTGCTGGAGG GAGTGATGGC AGCACGGGGA CAACTGGGAC CCACTTGCCT CT - #CATCCCTC   
 840                                                                      
- CTGGGGCAGC TTTCTGGACA GGTCCGTCTC CTCCTTGGGG CCCTGCAGAG CC - #TCCTTGGA   
 900                                                                      
# 918              AG                                                     
- (2) INFORMATION FOR SEQ ID NO:127:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 918 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:127:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGC TCACAAGGAT CCCAATGCCA TCTTCCTGAG CT - #TCCAACAC   
 480                                                                      
- CTGCTCCGAG GAAAGGTGCG TTTCCTGATG CTTGTAGGAG GGTCCACCCT CT - #GCGTCAGG   
 540                                                                      
- GAATTCGGCG GCAACATGGC GTCTCCCGCT CCGCCTGCTT GTGACCTCCG AG - #TCCTCAGT   
 600                                                                      
- AAACTGCTTC GTGACTCCCA TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AG - #AGGTTCAC   
 660                                                                      
- CCTTTGCCTA CACCTGTCCT GCTGCCTGCT GTGGACTTTA GCTTGGGAGA AT - #GGAAAACC   
 720                                                                      
- CAGATGGAGG AGACCAAGGC ACAGGACATT CTGGGAGCAG TGACCCTTCT GC - #TGGAGGGA   
 780                                                                      
- GTGATGGCAG CACGGGGACA ACTGGGACCC ACTTGCCTCT CATCCCTCCT GG - #GGCAGCTT   
 840                                                                      
- TCTGGACAGG TCCGTCTCCT CCTTGGGGCC CTGCAGAGCC TCCTTGGAAC CC - #AGCTTCCT   
 900                                                                      
# 918              CA                                                     
- (2) INFORMATION FOR SEQ ID NO:128:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 918 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:128:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CC - #TGCTCCGA   
 480                                                                      
- GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GG - #AATTCGGC   
 540                                                                      
- GGCAACATGG CGTCTCCCGC TCCGCCTGCT TGTGACCTCC GAGTCCTCAG TA - #AACTGCTT   
 600                                                                      
- CGTGACTCCC ATGTCCTTCA CAGCAGACTG AGCCAGTGCC CAGAGGTTCA CC - #CTTTGCCT   
 660                                                                      
- ACACCTGTCC TGCTGCCTGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CC - #AGATGGAG   
 720                                                                      
- GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AG - #TGATGGCA   
 780                                                                      
- GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TT - #CTGGACAG   
 840                                                                      
- GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGCTTCC TC - #CACAGGGC   
 900                                                                      
# 918              AG                                                     
- (2) INFORMATION FOR SEQ ID NO:129:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 918 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:129:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGC CATCTTCCTG AGCTTCCAAC ACCTGCTCCG AG - #GAAAGGTG   
 480                                                                      
- CGTTTCCTGA TGCTTGTAGG AGGGTCCACC CTCTGCGTCA GGGAATTCGG CG - #GCAACATG   
 540                                                                      
- GCGTCTCCCG CTCCGCCTGC TTGTGACCTC CGAGTCCTCA GTAAACTGCT TC - #GTGACTCC   
 600                                                                      
- CATGTCCTTC ACAGCAGACT GAGCCAGTGC CCAGAGGTTC ACCCTTTGCC TA - #CACCTGTC   
 660                                                                      
- CTGCTGCCTG CTGTGGACTT TAGCTTGGGA GAATGGAAAA CCCAGATGGA GG - #AGACCAAG   
 720                                                                      
- GCACAGGACA TTCTGGGAGC AGTGACCCTT CTGCTGGAGG GAGTGATGGC AG - #CACGGGGA   
 780                                                                      
- CAACTGGGAC CCACTTGCCT CTCATCCCTC CTGGGGCAGC TTTCTGGACA GG - #TCCGTCTC   
 840                                                                      
- CTCCTTGGGG CCCTGCAGAG CCTCCTTGGA ACCCAGCTTC CTCCACAGGG CA - #GGACCACA   
 900                                                                      
# 918              AT                                                     
- (2) INFORMATION FOR SEQ ID NO:130:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 915 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:130:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGA GGTTCACCCT TTGCCTACAC CTGTCCTGCT GC - #CTGCTGTG   
 480                                                                      
- GACTTTAGCT TGGGAGAATG GAAAACCCAG ATGGAGGAGA CCAAGGCACA GG - #ACATTCTG   
 540                                                                      
- GGAGCAGTGA CCCTTCTGCT GGAGGGAGTG ATGGCAGCAC GGGGACAACT GG - #GACCCACT   
 600                                                                      
- TGCCTCTCAT CCCTCCTGGG GCAGCTTTCT GGACAGGTCC GTCTCCTCCT TG - #GGGCCCTG   
 660                                                                      
- CAGAGCCTCC TTGGAACCCA GCTTCCTCCA CAGGGCAGGA CCACAGCTCA CA - #AGGATCCC   
 720                                                                      
- AATGCCATCT TCCTGAGCTT CCAACACCTG CTCCGAGGAA AGGTGCGTTT CC - #TGATGCTT   
 780                                                                      
- GTAGGAGGGT CCACCCTCTG CGTCAGGGAA TTCGGCAACA TGGCGTCTCC CG - #CTCCGCCT   
 840                                                                      
- GCTTGTGACC TCCGAGTCCT CAGTAAACTG CTTCGTGACT CCCATGTCCT TC - #ACAGCAGA   
 900                                                                      
#   915                                                                   
- (2) INFORMATION FOR SEQ ID NO:131:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 915 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:131:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGTT GCCTACACCT GTCCTGCTGC CTGCTGTGGA CT - #TTAGCTTG   
 480                                                                      
- GGAGAATGGA AAACCCAGAT GGAGGAGACC AAGGCACAGG ACATTCTGGG AG - #CAGTGACC   
 540                                                                      
- CTTCTGCTGG AGGGAGTGAT GGCAGCACGG GGACAACTGG GACCCACTTG CC - #TCTCATCC   
 600                                                                      
- CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT CTCCTCCTTG GGGCCCTGCA GA - #GCCTCCTT   
 660                                                                      
- GGAACCCAGC TTCCTCCACA GGGCAGGACC ACAGCTCACA AGGATCCCAA TG - #CCATCTTC   
 720                                                                      
- CTGAGCTTCC AACACCTGCT CCGAGGAAAG GTGCGTTTCC TGATGCTTGT AG - #GAGGGTCC   
 780                                                                      
- ACCCTCTGCG TCAGGGAATT CGGCAACATG GCGTCTCCCG CTCCGCCTGC TT - #GTGACCTC   
 840                                                                      
- CGAGTCCTCA GTAAACTGCT TCGTGACTCC CATGTCCTTC ACAGCAGACT GA - #GCCAGTGC   
 900                                                                      
#   915                                                                   
- (2) INFORMATION FOR SEQ ID NO:132:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 915 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:132:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGT CCTGCTGCCT GCTGTGGACT TTAGCTTGGG AG - #AATGGAAA   
 480                                                                      
- ACCCAGATGG AGGAGACCAA GGCACAGGAC ATTCTGGGAG CAGTGACCCT TC - #TGCTGGAG   
 540                                                                      
- GGAGTGATGG CAGCACGGGG ACAACTGGGA CCCACTTGCC TCTCATCCCT CC - #TGGGGCAG   
 600                                                                      
- CTTTCTGGAC AGGTCCGTCT CCTCCTTGGG GCCCTGCAGA GCCTCCTTGG AA - #CCCAGCTT   
 660                                                                      
- CCTCCACAGG GCAGGACCAC AGCTCACAAG GATCCCAATG CCATCTTCCT GA - #GCTTCCAA   
 720                                                                      
- CACCTGCTCC GAGGAAAGGT GCGTTTCCTG ATGCTTGTAG GAGGGTCCAC CC - #TCTGCGTC   
 780                                                                      
- AGGGAATTCG GCAACATGGC GTCTCCCGCT CCGCCTGCTT GTGACCTCCG AG - #TCCTCAGT   
 840                                                                      
- AAACTGCTTC GTGACTCCCA TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AG - #AGGTTCAC   
 900                                                                      
#   915                                                                   
- (2) INFORMATION FOR SEQ ID NO:133:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 915 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:133:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CC - #AGATGGAG   
 480                                                                      
- GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AG - #TGATGGCA   
 540                                                                      
- GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TT - #CTGGACAG   
 600                                                                      
- GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGCTTCC TC - #CACAGGGC   
 660                                                                      
- AGGACCACAG CTCACAAGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CC - #TGCTCCGA   
 720                                                                      
- GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GG - #AATTCGGC   
 780                                                                      
- AACATGGCGT CTCCCGCTCC GCCTGCTTGT GACCTCCGAG TCCTCAGTAA AC - #TGCTTCGT   
 840                                                                      
- GACTCCCATG TCCTTCACAG CAGACTGAGC CAGTGCCCAG AGGTTCACCC TT - #TGCCTACA   
 900                                                                      
#   915                                                                   
- (2) INFORMATION FOR SEQ ID NO:134:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 915 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:134:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGA CTTTAGCTTG GGAGAATGGA AAACCCAGAT GG - #AGGAGACC   
 480                                                                      
- AAGGCACAGG ACATTCTGGG AGCAGTGACC CTTCTGCTGG AGGGAGTGAT GG - #CAGCACGG   
 540                                                                      
- GGACAACTGG GACCCACTTG CCTCTCATCC CTCCTGGGGC AGCTTTCTGG AC - #AGGTCCGT   
 600                                                                      
- CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT GGAACCCAGC TTCCTCCACA GG - #GCAGGACC   
 660                                                                      
- ACAGCTCACA AGGATCCCAA TGCCATCTTC CTGAGCTTCC AACACCTGCT CC - #GAGGAAAG   
 720                                                                      
- GTGCGTTTCC TGATGCTTGT AGGAGGGTCC ACCCTCTGCG TCAGGGAATT CG - #GCAACATG   
 780                                                                      
- GCGTCTCCCG CTCCGCCTGC TTGTGACCTC CGAGTCCTCA GTAAACTGCT TC - #GTGACTCC   
 840                                                                      
- CATGTCCTTC ACAGCAGACT GAGCCAGTGC CCAGAGGTTC ACCCTTTGCC TA - #CACCTGTC   
 900                                                                      
#   915                                                                   
- (2) INFORMATION FOR SEQ ID NO:135:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 915 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:135:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGG AGAATGGAAA ACCCAGATGG AGGAGACCAA GG - #CACAGGAC   
 480                                                                      
- ATTCTGGGAG CAGTGACCCT TCTGCTGGAG GGAGTGATGG CAGCACGGGG AC - #AACTGGGA   
 540                                                                      
- CCCACTTGCC TCTCATCCCT CCTGGGGCAG CTTTCTGGAC AGGTCCGTCT CC - #TCCTTGGG   
 600                                                                      
- GCCCTGCAGA GCCTCCTTGG AACCCAGCTT CCTCCACAGG GCAGGACCAC AG - #CTCACAAG   
 660                                                                      
- GATCCCAATG CCATCTTCCT GAGCTTCCAA CACCTGCTCC GAGGAAAGGT GC - #GTTTCCTG   
 720                                                                      
- ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC AGGGAATTCG GCAACATGGC GT - #CTCCCGCT   
 780                                                                      
- CCGCCTGCTT GTGACCTCCG AGTCCTCAGT AAACTGCTTC GTGACTCCCA TG - #TCCTTCAC   
 840                                                                      
- AGCAGACTGA GCCAGTGCCC AGAGGTTCAC CCTTTGCCTA CACCTGTCCT GC - #TGCCTGCT   
 900                                                                      
#   915                                                                   
- (2) INFORMATION FOR SEQ ID NO:136:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 915 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:136:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGG ACCCACTTGC CTCTCATCCC TCCTGGGGCA GC - #TTTCTGGA   
 480                                                                      
- CAGGTCCGTC TCCTCCTTGG GGCCCTGCAG AGCCTCCTTG GAACCCAGCT TC - #CTCCACAG   
 540                                                                      
- GGCAGGACCA CAGCTCACAA GGATCCCAAT GCCATCTTCC TGAGCTTCCA AC - #ACCTGCTC   
 600                                                                      
- CGAGGAAAGG TGCGTTTCCT GATGCTTGTA GGAGGGTCCA CCCTCTGCGT CA - #GGGAATTC   
 660                                                                      
- GGCAACATGG CGTCTCCCGC TCCGCCTGCT TGTGACCTCC GAGTCCTCAG TA - #AACTGCTT   
 720                                                                      
- CGTGACTCCC ATGTCCTTCA CAGCAGACTG AGCCAGTGCC CAGAGGTTCA CC - #CTTTGCCT   
 780                                                                      
- ACACCTGTCC TGCTGCCTGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CC - #AGATGGAG   
 840                                                                      
- GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AG - #TGATGGCA   
 900                                                                      
#   915                                                                   
- (2) INFORMATION FOR SEQ ID NO:137:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 915 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:137:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGG AACCCAGCTT CCTCCACAGG GCAGGACCAC AG - #CTCACAAG   
 480                                                                      
- GATCCCAATG CCATCTTCCT GAGCTTCCAA CACCTGCTCC GAGGAAAGGT GC - #GTTTCCTG   
 540                                                                      
- ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC AGGGAATTCG GCAACATGGC GT - #CTCCCGCT   
 600                                                                      
- CCGCCTGCTT GTGACCTCCG AGTCCTCAGT AAACTGCTTC GTGACTCCCA TG - #TCCTTCAC   
 660                                                                      
- AGCAGACTGA GCCAGTGCCC AGAGGTTCAC CCTTTGCCTA CACCTGTCCT GC - #TGCCTGCT   
 720                                                                      
- GTGGACTTTA GCTTGGGAGA ATGGAAAACC CAGATGGAGG AGACCAAGGC AC - #AGGACATT   
 780                                                                      
- CTGGGAGCAG TGACCCTTCT GCTGGAGGGA GTGATGGCAG CACGGGGACA AC - #TGGGACCC   
 840                                                                      
- ACTTGCCTCT CATCCCTCCT GGGGCAGCTT TCTGGACAGG TCCGTCTCCT CC - #TTGGGGCC   
 900                                                                      
#   915                                                                   
- (2) INFORMATION FOR SEQ ID NO:138:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 915 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:138:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGG CAGGACCACA GCTCACAAGG ATCCCAATGC CA - #TCTTCCTG   
 480                                                                      
- AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG CGTTTCCTGA TGCTTGTAGG AG - #GGTCCACC   
 540                                                                      
- CTCTGCGTCA GGGAATTCGG CAACATGGCG TCTCCCGCTC CGCCTGCTTG TG - #ACCTCCGA   
 600                                                                      
- GTCCTCAGTA AACTGCTTCG TGACTCCCAT GTCCTTCACA GCAGACTGAG CC - #AGTGCCCA   
 660                                                                      
- GAGGTTCACC CTTTGCCTAC ACCTGTCCTG CTGCCTGCTG TGGACTTTAG CT - #TGGGAGAA   
 720                                                                      
- TGGAAAACCC AGATGGAGGA GACCAAGGCA CAGGACATTC TGGGAGCAGT GA - #CCCTTCTG   
 780                                                                      
- CTGGAGGGAG TGATGGCAGC ACGGGGACAA CTGGGACCCA CTTGCCTCTC AT - #CCCTCCTG   
 840                                                                      
- GGGCAGCTTT CTGGACAGGT CCGTCTCCTC CTTGGGGCCC TGCAGAGCCT CC - #TTGGAACC   
 900                                                                      
#   915                                                                   
- (2) INFORMATION FOR SEQ ID NO:139:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 915 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:139:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGC TCACAAGGAT CCCAATGCCA TCTTCCTGAG CT - #TCCAACAC   
 480                                                                      
- CTGCTCCGAG GAAAGGTGCG TTTCCTGATG CTTGTAGGAG GGTCCACCCT CT - #GCGTCAGG   
 540                                                                      
- GAATTCGGCA ACATGGCGTC TCCCGCTCCG CCTGCTTGTG ACCTCCGAGT CC - #TCAGTAAA   
 600                                                                      
- CTGCTTCGTG ACTCCCATGT CCTTCACAGC AGACTGAGCC AGTGCCCAGA GG - #TTCACCCT   
 660                                                                      
- TTGCCTACAC CTGTCCTGCT GCCTGCTGTG GACTTTAGCT TGGGAGAATG GA - #AAACCCAG   
 720                                                                      
- ATGGAGGAGA CCAAGGCACA GGACATTCTG GGAGCAGTGA CCCTTCTGCT GG - #AGGGAGTG   
 780                                                                      
- ATGGCAGCAC GGGGACAACT GGGACCCACT TGCCTCTCAT CCCTCCTGGG GC - #AGCTTTCT   
 840                                                                      
- GGACAGGTCC GTCTCCTCCT TGGGGCCCTG CAGAGCCTCC TTGGAACCCA GC - #TTCCTCCA   
 900                                                                      
#   915                                                                   
- (2) INFORMATION FOR SEQ ID NO:140:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 915 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:140:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CC - #TGCTCCGA   
 480                                                                      
- GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GG - #AATTCGGC   
 540                                                                      
- AACATGGCGT CTCCCGCTCC GCCTGCTTGT GACCTCCGAG TCCTCAGTAA AC - #TGCTTCGT   
 600                                                                      
- GACTCCCATG TCCTTCACAG CAGACTGAGC CAGTGCCCAG AGGTTCACCC TT - #TGCCTACA   
 660                                                                      
- CCTGTCCTGC TGCCTGCTGT GGACTTTAGC TTGGGAGAAT GGAAAACCCA GA - #TGGAGGAG   
 720                                                                      
- ACCAAGGCAC AGGACATTCT GGGAGCAGTG ACCCTTCTGC TGGAGGGAGT GA - #TGGCAGCA   
 780                                                                      
- CGGGGACAAC TGGGACCCAC TTGCCTCTCA TCCCTCCTGG GGCAGCTTTC TG - #GACAGGTC   
 840                                                                      
- CGTCTCCTCC TTGGGGCCCT GCAGAGCCTC CTTGGAACCC AGCTTCCTCC AC - #AGGGCAGG   
 900                                                                      
#   915                                                                   
- (2) INFORMATION FOR SEQ ID NO:141:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 915 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:141:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGC CATCTTCCTG AGCTTCCAAC ACCTGCTCCG AG - #GAAAGGTG   
 480                                                                      
- CGTTTCCTGA TGCTTGTAGG AGGGTCCACC CTCTGCGTCA GGGAATTCGG CA - #ACATGGCG   
 540                                                                      
- TCTCCCGCTC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TG - #ACTCCCAT   
 600                                                                      
- GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC AC - #CTGTCCTG   
 660                                                                      
- CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GA - #CCAAGGCA   
 720                                                                      
- CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC AC - #GGGGACAA   
 780                                                                      
- CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CC - #GTCTCCTC   
 840                                                                      
- CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GA - #CCACAGCT   
 900                                                                      
#   915                                                                   
- (2) INFORMATION FOR SEQ ID NO:142:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 921 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:142:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- GACTTCCAAA CCTGGAGAGC TTCGTAAGGG CTGTCAAGAA CTTAGAAAAT GC - #ATCAGGTA   
 180                                                                      
- TGAGGCAATT CTTCGTAATC TCCAACCATG TCTGCCCTCT GCCACGGCCG CA - #CCCTCTCG   
 240                                                                      
- CATCCAATCA TCATCAAGGC AGGTGACTGG CAAGAATTCC GGGAAAAACT GA - #CGTTCTAT   
 300                                                                      
- TGGTTACCCT TGAGCAAGCG CAGGAACAAC AGTACGTAGA GGGCGGTGGA GG - #CTCCCCGG   
 360                                                                      
- TAACCGTCTG GTCCAATCTC TACTATCAAC CCGTCTCCTC CGTCTAAAGA AT - #CTCATAAA   
 420                                                                      
- TCTCCAAACA TGGAGGTTCA CCCTTTGCCT ACACCTGTCC TGCTGCCTGC TG - #TGGACTTT   
 480                                                                      
- AGCTTGGGAG AATGGAAAAC CCAGATGGAG GAGACCAAGG CACAGGACAT TC - #TGGGAGCA   
 540                                                                      
- GTGACCCTTC TGCTGGAGGG AGTGATGGCA GCACGGGGAC AACTGGGACC CA - #CTTGCCTC   
 600                                                                      
- TCATCCCTCC TGGGGCAGCT TTCTGGACAG GTCCGTCTCC TCCTTGGGGC CC - #TGCAGAGC   
 660                                                                      
- CTCCTTGGAA CCCAGCTTCC TCCACAGGGC AGGACCACAG CTCACAAGGA TC - #CCAATGCC   
 720                                                                      
- ATCTTCCTGA GCTTCCAACA CCTGCTCCGA GGAAAGGTGC GTTTCCTGAT GC - #TTGTAGGA   
 780                                                                      
- GGGTCCACCC TCTGCGTCAG GGAATTCGGC GGCAACGGCG GCAACATGGC GT - #CCCCAGCG   
 840                                                                      
- CCGCCTGCTT GTGACCTCCG AGTCCTCAGT AAACTGCTTC GTGACTCCCA TG - #TCCTTCAC   
 900                                                                      
#                 921CC A                                                 
- (2) INFORMATION FOR SEQ ID NO:143:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:143:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGTT GCCTACACCT GTCCTGCTGC CTGCTGTGGA CT - #TTAGCTTG   
 480                                                                      
- GGAGAATGGA AAACCCAGAT GGAGGAGACC AAGGCACAGG ACATTCTGGG AG - #CAGTGACC   
 540                                                                      
- CTTCTGCTGG AGGGAGTGAT GGCAGCACGG GGACAACTGG GACCCACTTG CC - #TCTCATCC   
 600                                                                      
- CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT CTCCTCCTTG GGGCCCTGCA GA - #GCCTCCTT   
 660                                                                      
- GGAACCCAGC TTCCTCCACA GGGCAGGACC ACAGCTCACA AGGATCCCAA TG - #CCATCTTC   
 720                                                                      
- CTGAGCTTCC AACACCTGCT CCGAGGAAAG GTGCGTTTCC TGATGCTTGT AG - #GAGGGTCC   
 780                                                                      
- ACCCTCTGCG TCAGGGAATT CGGCGGCAAC GGCGGCAACA TGGCGTCCCC AG - #CGCCGCCT   
 840                                                                      
- GCTTGTGACC TCCGAGTCCT CAGTAAACTG CTTCGTGACT CCCATGTCCT TC - #ACAGCAGA   
 900                                                                      
#            927   AGGT TCACCCT                                           
- (2) INFORMATION FOR SEQ ID NO:144:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:144:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGT CCTGCTGCCT GCTGTGGACT TTAGCTTGGG AG - #AATGGAAA   
 480                                                                      
- ACCCAGATGG AGGAGACCAA GGCACAGGAC ATTCTGGGAG CAGTGACCCT TC - #TGCTGGAG   
 540                                                                      
- GGAGTGATGG CAGCACGGGG ACAACTGGGA CCCACTTGCC TCTCATCCCT CC - #TGGGGCAG   
 600                                                                      
- CTTTCTGGAC AGGTCCGTCT CCTCCTTGGG GCCCTGCAGA GCCTCCTTGG AA - #CCCAGCTT   
 660                                                                      
- CCTCCACAGG GCAGGACCAC AGCTCACAAG GATCCCAATG CCATCTTCCT GA - #GCTTCCAA   
 720                                                                      
- CACCTGCTCC GAGGAAAGGT GCGTTTCCTG ATGCTTGTAG GAGGGTCCAC CC - #TCTGCGTC   
 780                                                                      
- AGGGAATTCG GCGGCAACGG CGGCAACATG GCGTCCCCAG CGCCGCCTGC TT - #GTGACCTC   
 840                                                                      
- CGAGTCCTCA GTAAACTGCT TCGTGACTCC CATGTCCTTC ACAGCAGACT GA - #GCCAGTGC   
 900                                                                      
#            927   TGCC TACACCT                                           
- (2) INFORMATION FOR SEQ ID NO:145:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:145:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CC - #AGATGGAG   
 480                                                                      
- GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AG - #TGATGGCA   
 540                                                                      
- GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TT - #CTGGACAG   
 600                                                                      
- GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGCTTCC TC - #CACAGGGC   
 660                                                                      
- AGGACCACAG CTCACAAGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CC - #TGCTCCGA   
 720                                                                      
- GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GG - #AATTCGGC   
 780                                                                      
- GGCAACGGCG GCAACATGGC GTCCCCAGCG CCGCCTGCTT GTGACCTCCG AG - #TCCTCAGT   
 840                                                                      
- AAACTGCTTC GTGACTCCCA TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AG - #AGGTTCAC   
 900                                                                      
#            927   TCCT GCTGCCT                                           
- (2) INFORMATION FOR SEQ ID NO:146:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:146:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGA CTTTAGCTTG GGAGAATGGA AAACCCAGAT GG - #AGGAGACC   
 480                                                                      
- AAGGCACAGG ACATTCTGGG AGCAGTGACC CTTCTGCTGG AGGGAGTGAT GG - #CAGCACGG   
 540                                                                      
- GGACAACTGG GACCCACTTG CCTCTCATCC CTCCTGGGGC AGCTTTCTGG AC - #AGGTCCGT   
 600                                                                      
- CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT GGAACCCAGC TTCCTCCACA GG - #GCAGGACC   
 660                                                                      
- ACAGCTCACA AGGATCCCAA TGCCATCTTC CTGAGCTTCC AACACCTGCT CC - #GAGGAAAG   
 720                                                                      
- GTGCGTTTCC TGATGCTTGT AGGAGGGTCC ACCCTCTGCG TCAGGGAATT CG - #GCGGCAAC   
 780                                                                      
- GGCGGCAACA TGGCGTCCCC AGCGCCGCCT GCTTGTGACC TCCGAGTCCT CA - #GTAAACTG   
 840                                                                      
- CTTCGTGACT CCCATGTCCT TCACAGCAGA CTGAGCCAGT GCCCAGAGGT TC - #ACCCTTTG   
 900                                                                      
#            927   TGCC TGCTGTG                                           
- (2) INFORMATION FOR SEQ ID NO:147:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:147:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGG AGAATGGAAA ACCCAGATGG AGGAGACCAA GG - #CACAGGAC   
 480                                                                      
- ATTCTGGGAG CAGTGACCCT TCTGCTGGAG GGAGTGATGG CAGCACGGGG AC - #AACTGGGA   
 540                                                                      
- CCCACTTGCC TCTCATCCCT CCTGGGGCAG CTTTCTGGAC AGGTCCGTCT CC - #TCCTTGGG   
 600                                                                      
- GCCCTGCAGA GCCTCCTTGG AACCCAGCTT CCTCCACAGG GCAGGACCAC AG - #CTCACAAG   
 660                                                                      
- GATCCCAATG CCATCTTCCT GAGCTTCCAA CACCTGCTCC GAGGAAAGGT GC - #GTTTCCTG   
 720                                                                      
- ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC AGGGAATTCG GCGGCAACGG CG - #GCAACATG   
 780                                                                      
- GCGTCCCCAG CGCCGCCTGC TTGTGACCTC CGAGTCCTCA GTAAACTGCT TC - #GTGACTCC   
 840                                                                      
- CATGTCCTTC ACAGCAGACT GAGCCAGTGC CCAGAGGTTC ACCCTTTGCC TA - #CACCTGTC   
 900                                                                      
#            927   ACTT TAGCTTG                                           
- (2) INFORMATION FOR SEQ ID NO:148:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:148:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGG ACCCACTTGC CTCTCATCCC TCCTGGGGCA GC - #TTTCTGGA   
 480                                                                      
- CAGGTCCGTC TCCTCCTTGG GGCCCTGCAG AGCCTCCTTG GAACCCAGCT TC - #CTCCACAG   
 540                                                                      
- GGCAGGACCA CAGCTCACAA GGATCCCAAT GCCATCTTCC TGAGCTTCCA AC - #ACCTGCTC   
 600                                                                      
- CGAGGAAAGG TGCGTTTCCT GATGCTTGTA GGAGGGTCCA CCCTCTGCGT CA - #GGGAATTC   
 660                                                                      
- GGCGGCAACG GCGGCAACAT GGCGTCCCCA GCGCCGCCTG CTTGTGACCT CC - #GAGTCCTC   
 720                                                                      
- AGTAAACTGC TTCGTGACTC CCATGTCCTT CACAGCAGAC TGAGCCAGTG CC - #CAGAGGTT   
 780                                                                      
- CACCCTTTGC CTACACCTGT CCTGCTGCCT GCTGTGGACT TTAGCTTGGG AG - #AATGGAAA   
 840                                                                      
- ACCCAGATGG AGGAGACCAA GGCACAGGAC ATTCTGGGAG CAGTGACCCT TC - #TGCTGGAG   
 900                                                                      
#            927   GGGG ACAACTG                                           
- (2) INFORMATION FOR SEQ ID NO:149:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:149:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGG AACCCAGCTT CCTCCACAGG GCAGGACCAC AG - #CTCACAAG   
 480                                                                      
- GATCCCAATG CCATCTTCCT GAGCTTCCAA CACCTGCTCC GAGGAAAGGT GC - #GTTTCCTG   
 540                                                                      
- ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC AGGGAATTCG GCGGCAACGG CG - #GCAACATG   
 600                                                                      
- GCGTCCCCAG CGCCGCCTGC TTGTGACCTC CGAGTCCTCA GTAAACTGCT TC - #GTGACTCC   
 660                                                                      
- CATGTCCTTC ACAGCAGACT GAGCCAGTGC CCAGAGGTTC ACCCTTTGCC TA - #CACCTGTC   
 720                                                                      
- CTGCTGCCTG CTGTGGACTT TAGCTTGGGA GAATGGAAAA CCCAGATGGA GG - #AGACCAAG   
 780                                                                      
- GCACAGGACA TTCTGGGAGC AGTGACCCTT CTGCTGGAGG GAGTGATGGC AG - #CACGGGGA   
 840                                                                      
- CAACTGGGAC CCACTTGCCT CTCATCCCTC CTGGGGCAGC TTTCTGGACA GG - #TCCGTCTC   
 900                                                                      
#            927   AGAG CCTCCTT                                           
- (2) INFORMATION FOR SEQ ID NO:150:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:150:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGG CAGGACCACA GCTCACAAGG ATCCCAATGC CA - #TCTTCCTG   
 480                                                                      
- AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG CGTTTCCTGA TGCTTGTAGG AG - #GGTCCACC   
 540                                                                      
- CTCTGCGTCA GGGAATTCGG CGGCAACGGC GGCAACATGG CGTCCCCAGC GC - #CGCCTGCT   
 600                                                                      
- TGTGACCTCC GAGTCCTCAG TAAACTGCTT CGTGACTCCC ATGTCCTTCA CA - #GCAGACTG   
 660                                                                      
- AGCCAGTGCC CAGAGGTTCA CCCTTTGCCT ACACCTGTCC TGCTGCCTGC TG - #TGGACTTT   
 720                                                                      
- AGCTTGGGAG AATGGAAAAC CCAGATGGAG GAGACCAAGG CACAGGACAT TC - #TGGGAGCA   
 780                                                                      
- GTGACCCTTC TGCTGGAGGG AGTGATGGCA GCACGGGGAC AACTGGGACC CA - #CTTGCCTC   
 840                                                                      
- TCATCCCTCC TGGGGCAGCT TTCTGGACAG GTCCGTCTCC TCCTTGGGGC CC - #TGCAGAGC   
 900                                                                      
#            927   TTCC TCCACAG                                           
- (2) INFORMATION FOR SEQ ID NO:151:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:151:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGC TCACAAGGAT CCCAATGCCA TCTTCCTGAG CT - #TCCAACAC   
 480                                                                      
- CTGCTCCGAG GAAAGGTGCG TTTCCTGATG CTTGTAGGAG GGTCCACCCT CT - #GCGTCAGG   
 540                                                                      
- GAATTCGGCG GCAACGGCGG CAACATGGCG TCCCCAGCGC CGCCTGCTTG TG - #ACCTCCGA   
 600                                                                      
- GTCCTCAGTA AACTGCTTCG TGACTCCCAT GTCCTTCACA GCAGACTGAG CC - #AGTGCCCA   
 660                                                                      
- GAGGTTCACC CTTTGCCTAC ACCTGTCCTG CTGCCTGCTG TGGACTTTAG CT - #TGGGAGAA   
 720                                                                      
- TGGAAAACCC AGATGGAGGA GACCAAGGCA CAGGACATTC TGGGAGCAGT GA - #CCCTTCTG   
 780                                                                      
- CTGGAGGGAG TGATGGCAGC ACGGGGACAA CTGGGACCCA CTTGCCTCTC AT - #CCCTCCTG   
 840                                                                      
- GGGCAGCTTT CTGGACAGGT CCGTCTCCTC CTTGGGGCCC TGCAGAGCCT CC - #TTGGAACC   
 900                                                                      
#            927   GCAG GACCACA                                           
- (2) INFORMATION FOR SEQ ID NO:152:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:152:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CC - #TGCTCCGA   
 480                                                                      
- GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GG - #AATTCGGC   
 540                                                                      
- GGCAACGGCG GCAACATGGC GTCCCCAGCG CCGCCTGCTT GTGACCTCCG AG - #TCCTCAGT   
 600                                                                      
- AAACTGCTTC GTGACTCCCA TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AG - #AGGTTCAC   
 660                                                                      
- CCTTTGCCTA CACCTGTCCT GCTGCCTGCT GTGGACTTTA GCTTGGGAGA AT - #GGAAAACC   
 720                                                                      
- CAGATGGAGG AGACCAAGGC ACAGGACATT CTGGGAGCAG TGACCCTTCT GC - #TGGAGGGA   
 780                                                                      
- GTGATGGCAG CACGGGGACA ACTGGGACCC ACTTGCCTCT CATCCCTCCT GG - #GGCAGCTT   
 840                                                                      
- TCTGGACAGG TCCGTCTCCT CCTTGGGGCC CTGCAGAGCC TCCTTGGAAC CC - #AGCTTCCT   
 900                                                                      
#            927   CAGC TCACAAG                                           
- (2) INFORMATION FOR SEQ ID NO:153:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 927 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:153:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGC CATCTTCCTG AGCTTCCAAC ACCTGCTCCG AG - #GAAAGGTG   
 480                                                                      
- CGTTTCCTGA TGCTTGTAGG AGGGTCCACC CTCTGCGTCA GGGAATTCGG CG - #GCAACGGC   
 540                                                                      
- GGCAACATGG CGTCCCCAGC GCCGCCTGCT TGTGACCTCC GAGTCCTCAG TA - #AACTGCTT   
 600                                                                      
- CGTGACTCCC ATGTCCTTCA CAGCAGACTG AGCCAGTGCC CAGAGGTTCA CC - #CTTTGCCT   
 660                                                                      
- ACACCTGTCC TGCTGCCTGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CC - #AGATGGAG   
 720                                                                      
- GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AG - #TGATGGCA   
 780                                                                      
- GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TT - #CTGGACAG   
 840                                                                      
- GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGCTTCC TC - #CACAGGGC   
 900                                                                      
#            927   AGGA TCCCAAT                                           
- (2) INFORMATION FOR SEQ ID NO:154:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 906 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:154:                           
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
  60                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CC - #GAAACCTT   
 120                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
 180                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
 240                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
 300                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
 360                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
 420                                                                      
- CATAAATCTC CAAACATGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CC - #TGCTCCGA   
 480                                                                      
- GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GG - #AATTCGGC   
 540                                                                      
- GGCAACATGG CGTCTCCCGC TCCGCCTGCT TGTGACCTCC GAGTCCTCAG TA - #AACTGCTT   
 600                                                                      
- CGTGACTCCC ATGTCCTTCA CAGCAGACTG AGCCAGTGCC CAGAGGTTCA CC - #CTTTGCCT   
 660                                                                      
- ACACCTGTCC TGCTGCCTGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CC - #AGATGGAG   
 720                                                                      
- GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AG - #TGATGGCA   
 780                                                                      
- GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TT - #CTGGACAG   
 840                                                                      
- GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGGGCAG GA - #CCACAGCT   
 900                                                                      
#          906                                                            
- (2) INFORMATION FOR SEQ ID NO:155:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 993 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:155:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GTCTTACAAG CTGTGCCACC CCGAGGAGCT GG - #TGCTGCTC   
 480                                                                      
- GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GG - #CCCTGCAG   
 540                                                                      
- CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GC - #TCCTGCAG   
 600                                                                      
- GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GC - #TGGACGTC   
 660                                                                      
- GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CC - #CTGCCCTG   
 720                                                                      
- CAGCCCACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GG - #CAGGAGGG   
 780                                                                      
- GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TC - #TACGCCAC   
 840                                                                      
- CTTGCGCAGC CCGGCGGCGG CTCTGACATG GCTACACCAT TAGGCCCTGC CA - #GCTCCCTG   
 900                                                                      
- CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGGA AGATCCAGGG CG - #ATGGCGCA   
 960                                                                      
#        993       TGTG TGCCACCTAA TAA                                    
- (2) INFORMATION FOR SEQ ID NO:156:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 993 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:156:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GTCTCCCGAG TTGGGTCCCA CCTTGGACAC AC - #TGCAGCTG   
 480                                                                      
- GACGTCGCCG ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AA - #TGGCCCCT   
 540                                                                      
- GCCCTGCAGC CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GC - #GCCGGGCA   
 600                                                                      
- GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CC - #GCGTTCTA   
 660                                                                      
- CGCCACCTTG CGCAGCCCGG CGGCGGCTCT GACATGGCTA CACCATTAGG CC - #CTGCCAGC   
 720                                                                      
- TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG TGAGGAAGAT CC - #AGGGCGAT   
 780                                                                      
- GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC CG - #AGGAGCTG   
 840                                                                      
- GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CC - #CCAGCCAG   
 900                                                                      
- GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CT - #ACCAGGGG   
 960                                                                      
#        993       AAGG GATATCCTAA TAA                                    
- (2) INFORMATION FOR SEQ ID NO:157:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 993 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:157:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GTCTTCTGCT TTCCAGCGCC GGGCAGGAGG GG - #TCCTGGTT   
 480                                                                      
- GCTAGCCATC TGCAGAGCTT CCTGGAGGTG TCGTACCGCG TTCTACGCCA CC - #TTGCGCAG   
 540                                                                      
- CCCGGCGGCG GCTCTGACAT GGCTACACCA TTAGGCCCTG CCAGCTCCCT GC - #CCCAGAGC   
 600                                                                      
- TTCCTGCTCA AGTCTTTAGA GCAAGTGAGG AAGATCCAGG GCGATGGCGC AG - #CGCTCCAG   
 660                                                                      
- GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GC - #TCGGACAC   
 720                                                                      
- TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GC - #AGCTGGCA   
 780                                                                      
- GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GC - #AGGCCCTG   
 840                                                                      
- GAAGGGATAT CCCCCGAGTT GGGTCCCACC TTGGACACAC TGCAGCTGGA CG - #TCGCCGAC   
 900                                                                      
- TTTGCCACCA CCATCTGGCA GCAGATGGAA GAACTGGGAA TGGCCCCTGC CC - #TGCAGCCC   
 960                                                                      
#        993       CGGC CTTCGCCTAA TAA                                    
- (2) INFORMATION FOR SEQ ID NO:158:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 993 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:158:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GTCTATGGCC CCTGCCCTGC AGCCCACCCA GG - #GTGCCATG   
 480                                                                      
- CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TA - #GCCATCTG   
 540                                                                      
- CAGAGCTTCC TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CG - #GCGGCGGC   
 600                                                                      
- TCTGACATGG CTACACCATT AGGCCCTGCC AGCTCCCTGC CCCAGAGCTT CC - #TGCTCAAG   
 660                                                                      
- TCTTTAGAGC AAGTGAGGAA GATCCAGGGC GATGGCGCAG CGCTCCAGGA GA - #AGCTGTGT   
 720                                                                      
- GCCACCTACA AGCTGTGCCA CCCCGAGGAG CTGGTGCTGC TCGGACACTC TC - #TGGGCATC   
 780                                                                      
- CCCTGGGCTC CCCTGAGCTC CTGCCCCAGC CAGGCCCTGC AGCTGGCAGG CT - #GCTTGAGC   
 840                                                                      
- CAACTCCATA GCGGCCTTTT CCTCTACCAG GGGCTCCTGC AGGCCCTGGA AG - #GGATATCC   
 900                                                                      
- CCCGAGTTGG GTCCCACCTT GGACACACTG CAGCTGGACG TCGCCGACTT TG - #CCACCACC   
 960                                                                      
#        993       AAGA ACTGGGATAA TAA                                    
- (2) INFORMATION FOR SEQ ID NO:159:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 993 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:159:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GTCTACCCAG GGTGCCATGC CGGCCTTCGC CT - #CTGCTTTC   
 480                                                                      
- CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GG - #AGGTGTCG   
 540                                                                      
- TACCGCGTTC TACGCCACCT TGCGCAGCCC GGCGGCGGCT CTGACATGGC TA - #CACCATTA   
 600                                                                      
- GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA AG - #TGAGGAAG   
 660                                                                      
- ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG CCACCTACAA GC - #TGTGCCAC   
 720                                                                      
- CCCGAGGAGC TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CC - #TGAGCTCC   
 780                                                                      
- TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG CG - #GCCTTTTC   
 840                                                                      
- CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TC - #CCACCTTG   
 900                                                                      
- GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA GA - #TGGAAGAA   
 960                                                                      
#        993       CCCT GCAGCCCTAA TAA                                    
- (2) INFORMATION FOR SEQ ID NO:160:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 1027 base                                           
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:160:                           
- ATGGCTACAC CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CA - #AGTCTTTA   
  60                                                                      
- GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GT - #GTGCCACC   
 120                                                                      
- TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CA - #TCCCCTGG   
 180                                                                      
- GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GA - #GCCAACTC   
 240                                                                      
- CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT AT - #CCCCCGAG   
 300                                                                      
- TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CA - #CCATCTGG   
 360                                                                      
- CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TG - #CCATGCCG   
 420                                                                      
- GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CC - #ATCTGCAG   
 480                                                                      
- AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCGG CG - #GCGGCTCT   
 540                                                                      
- GACATGGCTA CACCATTGGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GC - #TCAAGTCT   
 600                                                                      
- TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA GC - #TGTGTGCC   
 660                                                                      
- ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG GACACTCTCT GG - #GCATCCCC   
 720                                                                      
- TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CT - #TGAGCCAA   
 780                                                                      
- CTCCATAGCG GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GA - #TATCCCCC   
 840                                                                      
- GAGTTGGGTC CCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CA - #CCACCATC   
 900                                                                      
- TGGCAGCAGA TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCA TC - #CTGGTTGC   
 960                                                                      
- TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTT CTACGCCACC TT - #GCGCAGCC   
1020                                                                      
#        1027                                                             
- (2) INFORMATION FOR SEQ ID NO:161:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 155 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:161:                           
- Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Va - #l Leu Ser Lys Leu Leu     
#                15                                                       
- Arg Asp Ser His Val Leu His Ser Arg Leu Se - #r Gln Cys Pro Glu Val     
#            30                                                           
- His Pro Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
#        45                                                               
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#    60                                                                   
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#80                                                                       
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#                95                                                       
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Leu     
#           110                                                           
- Pro Pro Gln Gly Arg Thr Thr Ala His Lys As - #p Pro Asn Ala Ile Phe     
#       125                                                               
- Leu Ser Phe Gln His Leu Leu Arg Gly Lys Va - #l Arg Phe Leu Met Leu     
#   140                                                                   
- Val Gly Gly Ser Thr Leu Cys Val Arg Glu Ph - #e                         
145                 1 - #50                 1 - #55                       
- (2) INFORMATION FOR SEQ ID NO:162:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 309 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:162:                           
- Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Va - #l Leu Ser Lys Leu Leu     
#                15                                                       
- Arg Asp Ser His Val Leu His Ser Arg Leu Se - #r Gln Cys Pro Glu Val     
#            30                                                           
- His Pro Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
#        45                                                               
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#    60                                                                   
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#80                                                                       
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#                95                                                       
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Leu     
#           110                                                           
- Pro Pro Gln Gly Arg Thr Thr Ala His Lys As - #p Pro Asn Ala Ile Phe     
#       125                                                               
- Leu Ser Phe Gln His Leu Leu Arg Gly Lys Va - #l Arg Phe Leu Met Leu     
#   140                                                                   
- Val Gly Gly Ser Thr Leu Cys Val Arg Glu Ph - #e Gly Gly Asn Met Ala     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Va - #l Leu Ser Lys Leu Leu     
#               175                                                       
- Arg Asp Ser His Val Leu His Ser Arg Leu Se - #r Gln Cys Pro Glu Val     
#           190                                                           
- His Pro Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
#       205                                                               
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#   220                                                                   
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#               255                                                       
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Gly     
#           270                                                           
- Arg Thr Thr Ala His Lys Asp Pro Asn Ala Il - #e Phe Leu Ser Phe Gln     
#       285                                                               
- His Leu Leu Arg Gly Lys Val Arg Phe Leu Me - #t Leu Val Gly Gly Ser     
#   300                                                                   
- Thr Leu Cys Val Arg                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:163:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 312 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:163:                           
- Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Va - #l Leu Ser Lys Leu Leu     
#                15                                                       
- Arg Asp Ser His Val Leu His Ser Arg Leu Se - #r Gln Cys Pro Glu Val     
#            30                                                           
- His Pro Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
#        45                                                               
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#    60                                                                   
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#80                                                                       
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#                95                                                       
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Leu     
#           110                                                           
- Pro Pro Gln Gly Arg Thr Thr Ala His Lys As - #p Pro Asn Ala Ile Phe     
#       125                                                               
- Leu Ser Phe Gln His Leu Leu Arg Gly Lys Va - #l Arg Phe Leu Met Leu     
#   140                                                                   
- Val Gly Gly Ser Thr Leu Cys Val Arg Glu Ph - #e Gly Asn Met Ala Ser     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Le - #u Ser Lys Leu Leu Arg     
#               175                                                       
- Asp Ser His Val Leu His Ser Arg Leu Ser Gl - #n Cys Pro Glu Val His     
#           190                                                           
- Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Va - #l Asp Phe Ser Leu Gly     
#       205                                                               
- Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Al - #a Gln Asp Ile Leu Gly     
#   220                                                                   
- Ala Val Thr Leu Leu Leu Glu Gly Val Met Al - #a Ala Arg Gly Gln Leu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gl - #n Leu Ser Gly Gln Val     
#               255                                                       
- Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Le - #u Gly Thr Gln Leu Pro     
#           270                                                           
- Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pr - #o Asn Ala Ile Phe Leu     
#       285                                                               
- Ser Phe Gln His Leu Leu Arg Gly Lys Val Ar - #g Phe Leu Met Leu Val     
#   300                                                                   
- Gly Gly Ser Thr Leu Cys Val Arg                                         
305                 3 - #10                                               
- (2) INFORMATION FOR SEQ ID NO:164:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 313 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:164:                           
- Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Va - #l Leu Ser Lys Leu Leu     
#                15                                                       
- Arg Asp Ser His Val Leu His Ser Arg Leu Se - #r Gln Cys Pro Glu Val     
#            30                                                           
- His Pro Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
#        45                                                               
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#    60                                                                   
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#80                                                                       
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#                95                                                       
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Leu     
#           110                                                           
- Pro Pro Gln Gly Arg Thr Thr Ala His Lys As - #p Pro Asn Ala Ile Phe     
#       125                                                               
- Leu Ser Phe Gln His Leu Leu Arg Gly Lys Va - #l Arg Phe Leu Met Leu     
#   140                                                                   
- Val Gly Gly Ser Thr Leu Cys Val Arg Glu Ph - #e Gly Gly Asn Met Ala     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Va - #l Leu Ser Lys Leu Leu     
#               175                                                       
- Arg Asp Ser His Val Leu His Ser Arg Leu Se - #r Gln Cys Pro Glu Val     
#           190                                                           
- His Pro Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
#       205                                                               
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#   220                                                                   
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#               255                                                       
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Leu     
#           270                                                           
- Pro Pro Gln Gly Arg Thr Thr Ala His Lys As - #p Pro Asn Ala Ile Phe     
#       285                                                               
- Leu Ser Phe Gln His Leu Leu Arg Gly Lys Va - #l Arg Phe Leu Met Leu     
#   300                                                                   
- Val Gly Gly Ser Thr Leu Cys Val Arg                                     
305                 3 - #10                                               
- (2) INFORMATION FOR SEQ ID NO:165:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 316 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:165:                           
- Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Va - #l Leu Ser Lys Leu Leu     
#                15                                                       
- Arg Asp Ser His Val Leu His Ser Arg Leu Se - #r Gln Cys Pro Glu Val     
#            30                                                           
- His Pro Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
#        45                                                               
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#    60                                                                   
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#80                                                                       
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#                95                                                       
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Leu     
#           110                                                           
- Pro Pro Gln Gly Arg Thr Thr Ala His Lys As - #p Pro Asn Ala Ile Phe     
#       125                                                               
- Leu Ser Phe Gln His Leu Leu Arg Gly Lys Va - #l Arg Phe Leu Met Leu     
#   140                                                                   
- Val Gly Gly Ser Thr Leu Cys Val Arg Glu Ph - #e Gly Gly Asn Gly Gly     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Asn Met Ala Ser Pro Ala Pro Pro Ala Cys As - #p Leu Arg Val Leu Ser     
#               175                                                       
- Lys Leu Leu Arg Asp Ser His Val Leu His Se - #r Arg Leu Ser Gln Cys     
#           190                                                           
- Pro Glu Val His Pro Leu Pro Thr Pro Val Le - #u Leu Pro Ala Val Asp     
#       205                                                               
- Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Gl - #u Glu Thr Lys Ala Gln     
#   220                                                                   
- Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Gl - #u Gly Val Met Ala Ala     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Se - #r Leu Leu Gly Gln Leu     
#               255                                                       
- Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Le - #u Gln Ser Leu Leu Gly     
#           270                                                           
- Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Al - #a His Lys Asp Pro Asn     
#       285                                                               
- Ala Ile Phe Leu Ser Phe Gln His Leu Leu Ar - #g Gly Lys Val Arg Phe     
#   300                                                                   
- Leu Met Leu Val Gly Gly Ser Thr Leu Cys Va - #l Arg                     
305                 3 - #10                 3 - #15                       
- (2) INFORMATION FOR SEQ ID NO:166:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 302 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:166:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gl - #y Ser Gly Gly Gly Ser     
#       125                                                               
- Asn Met Ala Tyr Lys Leu Cys His Pro Glu Gl - #u Leu Val Leu Leu Gly     
#   140                                                                   
- His Ser Leu Gly Ile Pro Trp Ala Pro Leu Se - #r Ser Cys Pro Ser Gln     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Le - #u His Ser Gly Leu Phe     
#               175                                                       
- Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gl - #y Ile Ser Pro Glu Leu     
#           190                                                           
- Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Va - #l Ala Asp Phe Ala Thr     
#       205                                                               
- Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Me - #t Ala Pro Ala Leu Gln     
#   220                                                                   
- Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Se - #r Ala Phe Gln Arg Arg     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ala Gly Gly Val Leu Val Ala Ser His Leu Gl - #n Ser Phe Leu Glu Val     
#               255                                                       
- Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pr - #o Ser Gly Gly Ser Gly     
#           270                                                           
- Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Gl - #u Gln Val Arg Lys Ile     
#       285                                                               
- Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Le - #u Cys Ala Thr             
#   300                                                                   
- (2) INFORMATION FOR SEQ ID NO:167:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 317 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:167:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pr - #o Ser Gly Pro Ile Ser     
#       125                                                               
- Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Se - #r His Lys Ser Pro Asn     
#   140                                                                   
- Met Ala Tyr Lys Leu Cys His Pro Glu Glu Le - #u Val Leu Leu Gly His     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Se - #r Cys Pro Ser Gln Ala     
#               175                                                       
- Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu Hi - #s Ser Gly Leu Phe Leu     
#           190                                                           
- Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Il - #e Ser Pro Glu Leu Gly     
#       205                                                               
- Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Al - #a Asp Phe Ala Thr Thr     
#   220                                                                   
- Ile Trp Gln Gln Met Glu Glu Leu Gly Met Al - #a Pro Ala Leu Gln Pro     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Al - #a Phe Gln Arg Arg Ala     
#               255                                                       
- Gly Gly Val Leu Val Ala Ser His Leu Gln Se - #r Phe Leu Glu Val Ser     
#           270                                                           
- Tyr Arg Val Leu Arg His Leu Ala Gln Pro Se - #r Gly Gly Ser Gly Gly     
#       285                                                               
- Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gl - #n Val Arg Lys Ile Gln     
#   300                                                                   
- Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cy - #s Ala Thr                 
305                 3 - #10                 3 - #15                       
- (2) INFORMATION FOR SEQ ID NO:168:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 302 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:168:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gl - #y Ser Gly Gly Gly Ser     
#       125                                                               
- Asn Met Ala Pro Glu Leu Gly Pro Thr Leu As - #p Thr Leu Gln Leu Asp     
#   140                                                                   
- Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gl - #n Met Glu Glu Leu Gly     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Al - #a Met Pro Ala Phe Ala     
#               175                                                       
- Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Le - #u Val Ala Ser His Leu     
#           190                                                           
- Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Le - #u Arg His Leu Ala Gln     
#       205                                                               
- Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Ph - #e Leu Leu Lys Ser Leu     
#   220                                                                   
- Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Al - #a Ala Leu Gln Glu Lys     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Gl - #u Glu Leu Val Leu Leu     
#               255                                                       
- Gly His Ser Leu Gly Ile Pro Trp Ala Pro Le - #u Ser Ser Cys Pro Ser     
#           270                                                           
- Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gl - #n Leu His Ser Gly Leu     
#       285                                                               
- Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Gl - #u Gly Ile Ser             
#   300                                                                   
- (2) INFORMATION FOR SEQ ID NO:169:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 317 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:169:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pr - #o Ser Gly Pro Ile Ser     
#       125                                                               
- Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Se - #r His Lys Ser Pro Asn     
#   140                                                                   
- Met Ala Pro Glu Leu Gly Pro Thr Leu Asp Th - #r Leu Gln Leu Asp Val     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Me - #t Glu Glu Leu Gly Met     
#               175                                                       
- Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Me - #t Pro Ala Phe Ala Ser     
#           190                                                           
- Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Va - #l Ala Ser His Leu Gln     
#       205                                                               
- Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Ar - #g His Leu Ala Gln Pro     
#   220                                                                   
- Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Le - #u Leu Lys Ser Leu Glu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Al - #a Leu Gln Glu Lys Leu     
#               255                                                       
- Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Gl - #u Leu Val Leu Leu Gly     
#           270                                                           
- His Ser Leu Gly Ile Pro Trp Ala Pro Leu Se - #r Ser Cys Pro Ser Gln     
#       285                                                               
- Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Le - #u His Ser Gly Leu Phe     
#   300                                                                   
- Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gl - #y Ile Ser                 
305                 3 - #10                 3 - #15                       
- (2) INFORMATION FOR SEQ ID NO:170:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 302 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:170:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gl - #y Ser Gly Gly Gly Ser     
#       125                                                               
- Asn Met Ala Met Ala Pro Ala Leu Gln Pro Th - #r Gln Gly Ala Met Pro     
#   140                                                                   
- Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gl - #y Gly Val Leu Val Ala     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ser His Leu Gln Ser Phe Leu Glu Val Ser Ty - #r Arg Val Leu Arg His     
#               175                                                       
- Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Se - #r Gln Ser Phe Leu Leu     
#           190                                                           
- Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gl - #y Asp Gly Ala Ala Leu     
#       205                                                               
- Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cy - #s His Pro Glu Glu Leu     
#   220                                                                   
- Val Leu Leu Gly His Ser Leu Gly Ile Pro Tr - #p Ala Pro Leu Ser Ser     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cy - #s Leu Ser Gln Leu His     
#               255                                                       
- Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gl - #n Ala Leu Glu Gly Ile     
#           270                                                           
- Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Le - #u Gln Leu Asp Val Ala     
#       285                                                               
- Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Gl - #u Glu Leu Gly             
#   300                                                                   
- (2) INFORMATION FOR SEQ ID NO:171:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 317 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:171:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pr - #o Ser Gly Pro Ile Ser     
#       125                                                               
- Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Se - #r His Lys Ser Pro Asn     
#   140                                                                   
- Met Ala Met Ala Pro Ala Leu Gln Pro Thr Gl - #n Gly Ala Met Pro Ala     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gl - #y Val Leu Val Ala Ser     
#               175                                                       
- His Leu Gln Ser Phe Leu Glu Val Ser Tyr Ar - #g Val Leu Arg His Leu     
#           190                                                           
- Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gl - #n Ser Phe Leu Leu Lys     
#       205                                                               
- Ser Leu Glu Gln Val Arg Lys Ile Gln Gly As - #p Gly Ala Ala Leu Gln     
#   220                                                                   
- Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys Hi - #s Pro Glu Glu Leu Val     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Leu Gly His Ser Leu Gly Ile Pro Trp Al - #a Pro Leu Ser Ser Cys     
#               255                                                       
- Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Le - #u Ser Gln Leu His Ser     
#           270                                                           
- Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Al - #a Leu Glu Gly Ile Ser     
#       285                                                               
- Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gl - #n Leu Asp Val Ala Asp     
#   300                                                                   
- Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Gl - #u Leu Gly                 
305                 3 - #10                 3 - #15                       
- (2) INFORMATION FOR SEQ ID NO:172:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 302 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:172:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gl - #y Ser Gly Gly Gly Ser     
#       125                                                               
- Asn Met Ala Thr Gln Gly Ala Met Pro Ala Ph - #e Ala Ser Ala Phe Gln     
#   140                                                                   
- Arg Arg Ala Gly Gly Val Leu Val Ala Ser Hi - #s Leu Gln Ser Phe Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Glu Val Ser Tyr Arg Val Leu Arg His Leu Al - #a Gln Pro Ser Gly Gly     
#               175                                                       
- Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Se - #r Leu Glu Gln Val Arg     
#           190                                                           
- Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Gl - #u Lys Leu Cys Ala Thr     
#       205                                                               
- Tyr Lys Leu Cys His Pro Glu Glu Leu Val Le - #u Leu Gly His Ser Leu     
#   220                                                                   
- Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pr - #o Ser Gln Ala Leu Gln     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gl - #y Leu Phe Leu Tyr Gln     
#               255                                                       
- Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pr - #o Glu Leu Gly Pro Thr     
#           270                                                           
- Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Ph - #e Ala Thr Thr Ile Trp     
#       285                                                               
- Gln Gln Met Glu Glu Leu Gly Met Ala Pro Al - #a Leu Gln Pro             
#   300                                                                   
- (2) INFORMATION FOR SEQ ID NO:173:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 317 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:173:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pr - #o Ser Gly Pro Ile Ser     
#       125                                                               
- Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Se - #r His Lys Ser Pro Asn     
#   140                                                                   
- Met Ala Thr Gln Gly Ala Met Pro Ala Phe Al - #a Ser Ala Phe Gln Arg     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Arg Ala Gly Gly Val Leu Val Ala Ser His Le - #u Gln Ser Phe Leu Glu     
#               175                                                       
- Val Ser Tyr Arg Val Leu Arg His Leu Ala Gl - #n Pro Ser Gly Gly Ser     
#           190                                                           
- Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Le - #u Glu Gln Val Arg Lys     
#       205                                                               
- Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Ly - #s Leu Cys Ala Thr Tyr     
#   220                                                                   
- Lys Leu Cys His Pro Glu Glu Leu Val Leu Le - #u Gly His Ser Leu Gly     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Se - #r Gln Ala Leu Gln Leu     
#               255                                                       
- Ala Gly Cys Leu Ser Gln Leu His Ser Gly Le - #u Phe Leu Tyr Gln Gly     
#           270                                                           
- Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Gl - #u Leu Gly Pro Thr Leu     
#       285                                                               
- Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Al - #a Thr Thr Ile Trp Gln     
#   300                                                                   
- Gln Met Glu Glu Leu Gly Met Ala Pro Ala Le - #u Gln Pro                 
305                 3 - #10                 3 - #15                       
- (2) INFORMATION FOR SEQ ID NO:174:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 302 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:174:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gl - #y Ser Gly Gly Gly Ser     
#       125                                                               
- Asn Met Ala Ser Ala Phe Gln Arg Arg Ala Gl - #y Gly Val Leu Val Ala     
#   140                                                                   
- Ser His Leu Gln Ser Phe Leu Glu Val Ser Ty - #r Arg Val Leu Arg His     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Se - #r Gln Ser Phe Leu Leu     
#               175                                                       
- Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gl - #y Asp Gly Ala Ala Leu     
#           190                                                           
- Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cy - #s His Pro Glu Glu Leu     
#       205                                                               
- Val Leu Leu Gly His Ser Leu Gly Ile Pro Tr - #p Ala Pro Leu Ser Ser     
#   220                                                                   
- Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cy - #s Leu Ser Gln Leu His     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gl - #n Ala Leu Glu Gly Ile     
#               255                                                       
- Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Le - #u Gln Leu Asp Val Ala     
#           270                                                           
- Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Gl - #u Glu Leu Gly Met Ala     
#       285                                                               
- Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pr - #o Ala Phe Ala             
#   300                                                                   
- (2) INFORMATION FOR SEQ ID NO:175:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 317 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:175:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pr - #o Ser Gly Pro Ile Ser     
#       125                                                               
- Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Se - #r His Lys Ser Pro Asn     
#   140                                                                   
- Met Ala Ser Ala Phe Gln Arg Arg Ala Gly Gl - #y Val Leu Val Ala Ser     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- His Leu Gln Ser Phe Leu Glu Val Ser Tyr Ar - #g Val Leu Arg His Leu     
#               175                                                       
- Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gl - #n Ser Phe Leu Leu Lys     
#           190                                                           
- Ser Leu Glu Gln Val Arg Lys Ile Gln Gly As - #p Gly Ala Ala Leu Gln     
#       205                                                               
- Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys Hi - #s Pro Glu Glu Leu Val     
#   220                                                                   
- Leu Leu Gly His Ser Leu Gly Ile Pro Trp Al - #a Pro Leu Ser Ser Cys     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Le - #u Ser Gln Leu His Ser     
#               255                                                       
- Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Al - #a Leu Glu Gly Ile Ser     
#           270                                                           
- Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gl - #n Leu Asp Val Ala Asp     
#       285                                                               
- Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Gl - #u Leu Gly Met Ala Pro     
#   300                                                                   
- Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Al - #a Phe Ala                 
305                 3 - #10                 3 - #15                       
- (2) INFORMATION FOR SEQ ID NO:176:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:176:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gl - #y Ser Gly Gly Gly Ser     
#       125                                                               
- Asn Met Ala Tyr Lys Leu Cys His Pro Glu Gl - #u Leu Val Leu Leu Gly     
#   140                                                                   
- His Ser Leu Gly Ile Pro Trp Ala Pro Leu Se - #r Ser Cys Pro Ser Gln     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Le - #u His Ser Gly Leu Phe     
#               175                                                       
- Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gl - #y Ile Ser Pro Glu Leu     
#           190                                                           
- Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Va - #l Ala Asp Phe Ala Thr     
#       205                                                               
- Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Me - #t Ala Pro Ala Leu Gln     
#   220                                                                   
- Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Se - #r Ala Phe Gln Arg Arg     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ala Gly Gly Val Leu Val Ala Ser His Leu Gl - #n Ser Phe Leu Glu Val     
#               255                                                       
- Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pr - #o Thr Pro Leu Gly Pro     
#           270                                                           
- Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Ly - #s Ser Leu Glu Gln Val     
#       285                                                               
- Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gl - #n Glu Lys Leu Cys Ala     
#   300                                                                   
- Thr                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:177:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 320 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:177:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pr - #o Ser Gly Pro Ile Ser     
#       125                                                               
- Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Se - #r His Lys Ser Pro Asn     
#   140                                                                   
- Met Ala Tyr Lys Leu Cys His Pro Glu Glu Le - #u Val Leu Leu Gly His     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Se - #r Cys Pro Ser Gln Ala     
#               175                                                       
- Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu Hi - #s Ser Gly Leu Phe Leu     
#           190                                                           
- Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Il - #e Ser Pro Glu Leu Gly     
#       205                                                               
- Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Al - #a Asp Phe Ala Thr Thr     
#   220                                                                   
- Ile Trp Gln Gln Met Glu Glu Leu Gly Met Al - #a Pro Ala Leu Gln Pro     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Al - #a Phe Gln Arg Arg Ala     
#               255                                                       
- Gly Gly Val Leu Val Ala Ser His Leu Gln Se - #r Phe Leu Glu Val Ser     
#           270                                                           
- Tyr Arg Val Leu Arg His Leu Ala Gln Pro Th - #r Pro Leu Gly Pro Ala     
#       285                                                               
- Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Se - #r Leu Glu Gln Val Arg     
#   300                                                                   
- Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Gl - #u Lys Leu Cys Ala Thr     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- (2) INFORMATION FOR SEQ ID NO:178:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:178:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gl - #y Ser Gly Gly Gly Ser     
#       125                                                               
- Asn Met Ala Pro Glu Leu Gly Pro Thr Leu As - #p Thr Leu Gln Leu Asp     
#   140                                                                   
- Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gl - #n Met Glu Glu Leu Gly     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Al - #a Met Pro Ala Phe Ala     
#               175                                                       
- Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Le - #u Val Ala Ser His Leu     
#           190                                                           
- Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Le - #u Arg His Leu Ala Gln     
#       205                                                               
- Pro Thr Pro Leu Gly Pro Ala Ser Ser Leu Pr - #o Gln Ser Phe Leu Leu     
#   220                                                                   
- Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gl - #y Asp Gly Ala Ala Leu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cy - #s His Pro Glu Glu Leu     
#               255                                                       
- Val Leu Leu Gly His Ser Leu Gly Ile Pro Tr - #p Ala Pro Leu Ser Ser     
#           270                                                           
- Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cy - #s Leu Ser Gln Leu His     
#       285                                                               
- Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gl - #n Ala Leu Glu Gly Ile     
#   300                                                                   
- Ser                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:179:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 320 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:179:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pr - #o Ser Gly Pro Ile Ser     
#       125                                                               
- Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Se - #r His Lys Ser Pro Asn     
#   140                                                                   
- Met Ala Pro Glu Leu Gly Pro Thr Leu Asp Th - #r Leu Gln Leu Asp Val     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Me - #t Glu Glu Leu Gly Met     
#               175                                                       
- Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Me - #t Pro Ala Phe Ala Ser     
#           190                                                           
- Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Va - #l Ala Ser His Leu Gln     
#       205                                                               
- Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Ar - #g His Leu Ala Gln Pro     
#   220                                                                   
- Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gl - #n Ser Phe Leu Leu Lys     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ser Leu Glu Gln Val Arg Lys Ile Gln Gly As - #p Gly Ala Ala Leu Gln     
#               255                                                       
- Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys Hi - #s Pro Glu Glu Leu Val     
#           270                                                           
- Leu Leu Gly His Ser Leu Gly Ile Pro Trp Al - #a Pro Leu Ser Ser Cys     
#       285                                                               
- Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Le - #u Ser Gln Leu His Ser     
#   300                                                                   
- Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Al - #a Leu Glu Gly Ile Ser     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- (2) INFORMATION FOR SEQ ID NO:180:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:180:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gl - #y Ser Gly Gly Gly Ser     
#       125                                                               
- Asn Met Ala Met Ala Pro Ala Leu Gln Pro Th - #r Gln Gly Ala Met Pro     
#   140                                                                   
- Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gl - #y Gly Val Leu Val Ala     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ser His Leu Gln Ser Phe Leu Glu Val Ser Ty - #r Arg Val Leu Arg His     
#               175                                                       
- Leu Ala Gln Pro Thr Pro Leu Gly Pro Ala Se - #r Ser Leu Pro Gln Ser     
#           190                                                           
- Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Ly - #s Ile Gln Gly Asp Gly     
#       205                                                               
- Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Ty - #r Lys Leu Cys His Pro     
#   220                                                                   
- Glu Glu Leu Val Leu Leu Gly His Ser Leu Gl - #y Ile Pro Trp Ala Pro     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Le - #u Ala Gly Cys Leu Ser     
#               255                                                       
- Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gl - #y Leu Leu Gln Ala Leu     
#           270                                                           
- Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Le - #u Asp Thr Leu Gln Leu     
#       285                                                               
- Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gl - #n Gln Met Glu Glu Leu     
#   300                                                                   
- Gly                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:181:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 320 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:181:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pr - #o Ser Gly Pro Ile Ser     
#       125                                                               
- Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Se - #r His Lys Ser Pro Asn     
#   140                                                                   
- Met Ala Met Ala Pro Ala Leu Gln Pro Thr Gl - #n Gly Ala Met Pro Ala     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gl - #y Val Leu Val Ala Ser     
#               175                                                       
- His Leu Gln Ser Phe Leu Glu Val Ser Tyr Ar - #g Val Leu Arg His Leu     
#           190                                                           
- Ala Gln Pro Thr Pro Leu Gly Pro Ala Ser Se - #r Leu Pro Gln Ser Phe     
#       205                                                               
- Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Il - #e Gln Gly Asp Gly Ala     
#   220                                                                   
- Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Ly - #s Leu Cys His Pro Glu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Glu Leu Val Leu Leu Gly His Ser Leu Gly Il - #e Pro Trp Ala Pro Leu     
#               255                                                       
- Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Al - #a Gly Cys Leu Ser Gln     
#           270                                                           
- Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Le - #u Leu Gln Ala Leu Glu     
#       285                                                               
- Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu As - #p Thr Leu Gln Leu Asp     
#   300                                                                   
- Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gl - #n Met Glu Glu Leu Gly     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- (2) INFORMATION FOR SEQ ID NO:182:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:182:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gl - #y Ser Gly Gly Gly Ser     
#       125                                                               
- Asn Met Ala Thr Gln Gly Ala Met Pro Ala Ph - #e Ala Ser Ala Phe Gln     
#   140                                                                   
- Arg Arg Ala Gly Gly Val Leu Val Ala Ser Hi - #s Leu Gln Ser Phe Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Glu Val Ser Tyr Arg Val Leu Arg His Leu Al - #a Gln Pro Thr Pro Leu     
#               175                                                       
- Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Le - #u Leu Lys Ser Leu Glu     
#           190                                                           
- Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Al - #a Leu Gln Glu Lys Leu     
#       205                                                               
- Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Gl - #u Leu Val Leu Leu Gly     
#   220                                                                   
- His Ser Leu Gly Ile Pro Trp Ala Pro Leu Se - #r Ser Cys Pro Ser Gln     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Le - #u His Ser Gly Leu Phe     
#               255                                                       
- Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gl - #y Ile Ser Pro Glu Leu     
#           270                                                           
- Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Va - #l Ala Asp Phe Ala Thr     
#       285                                                               
- Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Me - #t Ala Pro Ala Leu Gln     
#   300                                                                   
- Pro                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:183:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 320 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:183:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pr - #o Ser Gly Pro Ile Ser     
#       125                                                               
- Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Se - #r His Lys Ser Pro Asn     
#   140                                                                   
- Met Ala Thr Gln Gly Ala Met Pro Ala Phe Al - #a Ser Ala Phe Gln Arg     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Arg Ala Gly Gly Val Leu Val Ala Ser His Le - #u Gln Ser Phe Leu Glu     
#               175                                                       
- Val Ser Tyr Arg Val Leu Arg His Leu Ala Gl - #n Pro Thr Pro Leu Gly     
#           190                                                           
- Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Le - #u Lys Ser Leu Glu Gln     
#       205                                                               
- Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Le - #u Gln Glu Lys Leu Cys     
#   220                                                                   
- Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Le - #u Val Leu Leu Gly His     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Se - #r Cys Pro Ser Gln Ala     
#               255                                                       
- Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu Hi - #s Ser Gly Leu Phe Leu     
#           270                                                           
- Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Il - #e Ser Pro Glu Leu Gly     
#       285                                                               
- Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Al - #a Asp Phe Ala Thr Thr     
#   300                                                                   
- Ile Trp Gln Gln Met Glu Glu Leu Gly Met Al - #a Pro Ala Leu Gln Pro     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- (2) INFORMATION FOR SEQ ID NO:184:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:184:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gl - #y Ser Gly Gly Gly Ser     
#       125                                                               
- Asn Met Ala Ser Ala Phe Gln Arg Arg Ala Gl - #y Gly Val Leu Val Ala     
#   140                                                                   
- Ser His Leu Gln Ser Phe Leu Glu Val Ser Ty - #r Arg Val Leu Arg His     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Leu Ala Gln Pro Thr Pro Leu Gly Pro Ala Se - #r Ser Leu Pro Gln Ser     
#               175                                                       
- Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Ly - #s Ile Gln Gly Asp Gly     
#           190                                                           
- Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Ty - #r Lys Leu Cys His Pro     
#       205                                                               
- Glu Glu Leu Val Leu Leu Gly His Ser Leu Gl - #y Ile Pro Trp Ala Pro     
#   220                                                                   
- Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Le - #u Ala Gly Cys Leu Ser     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gl - #y Leu Leu Gln Ala Leu     
#               255                                                       
- Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Le - #u Asp Thr Leu Gln Leu     
#           270                                                           
- Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gl - #n Gln Met Glu Glu Leu     
#       285                                                               
- Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gl - #y Ala Met Pro Ala Phe     
#   300                                                                   
- Ala                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:185:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 320 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:185:                           
- Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Hi - #s His Leu Lys Arg Pro     
#                15                                                       
- Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu As - #n Asp Glu Asp Val Ser     
#            30                                                           
- Ile Leu Met Asp Arg Asn Leu Arg Leu Pro As - #n Leu Glu Ser Phe Val     
#        45                                                               
- Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gl - #y Ile Glu Ala Ile Leu     
#    60                                                                   
- Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Th - #r Ala Ala Pro Ser Arg     
#80                                                                       
- His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gl - #n Glu Phe Arg Glu Lys     
#                95                                                       
- Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Al - #a Gln Glu Gln Gln Tyr     
#           110                                                           
- Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pr - #o Ser Gly Pro Ile Ser     
#       125                                                               
- Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Se - #r His Lys Ser Pro Asn     
#   140                                                                   
- Met Ala Ser Ala Phe Gln Arg Arg Ala Gly Gl - #y Val Leu Val Ala Ser     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- His Leu Gln Ser Phe Leu Glu Val Ser Tyr Ar - #g Val Leu Arg His Leu     
#               175                                                       
- Ala Gln Pro Thr Pro Leu Gly Pro Ala Ser Se - #r Leu Pro Gln Ser Phe     
#           190                                                           
- Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Il - #e Gln Gly Asp Gly Ala     
#       205                                                               
- Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Ly - #s Leu Cys His Pro Glu     
#   220                                                                   
- Glu Leu Val Leu Leu Gly His Ser Leu Gly Il - #e Pro Trp Ala Pro Leu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Al - #a Gly Cys Leu Ser Gln     
#               255                                                       
- Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Le - #u Leu Gln Ala Leu Glu     
#           270                                                           
- Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu As - #p Thr Leu Gln Leu Asp     
#       285                                                               
- Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gl - #n Met Glu Glu Leu Gly     
#   300                                                                   
- Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Al - #a Met Pro Ala Phe Ala     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- (2) INFORMATION FOR SEQ ID NO:186:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 321 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:186:                           
- Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Va - #l Ser Ile Leu Met Asp     
#                15                                                       
- Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Ph - #e Val Arg Ala Val Lys     
#            30                                                           
- Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Il - #e Leu Arg Asn Leu Gln     
#        45                                                               
- Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Se - #r Arg His Pro Ile Ile     
#    60                                                                   
- Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Gl - #u Lys Leu Thr Phe Tyr     
#80                                                                       
- Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gl - #n Gly Gly Gly Ser Asn     
#                95                                                       
- Cys Ser Ile Met Ile Asp Glu Ile Ile His Hi - #s Leu Lys Arg Pro Pro     
#           110                                                           
- Ala Pro Leu Tyr Val Glu Gly Gly Gly Gly Se - #r Pro Gly Glu Pro Ser     
#       125                                                               
- Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pr - #o Ser Lys Glu Ser His     
#   140                                                                   
- Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Me - #t Pro Ala Phe Ala Ser     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Va - #l Ala Ser His Leu Gln     
#               175                                                       
- Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Ar - #g His Leu Ala Gln Pro     
#           190                                                           
- Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Le - #u Leu Lys Ser Leu Glu     
#       205                                                               
- Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Al - #a Leu Gln Glu Lys Leu     
#   220                                                                   
- Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Gl - #u Leu Val Leu Leu Gly     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- His Ser Leu Gly Ile Pro Trp Ala Pro Leu Se - #r Ser Cys Pro Ser Gln     
#               255                                                       
- Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Le - #u His Ser Gly Leu Phe     
#           270                                                           
- Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gl - #y Ile Ser Pro Glu Leu     
#       285                                                               
- Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Va - #l Ala Asp Phe Ala Thr     
#   300                                                                   
- Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Me - #t Ala Pro Ala Leu Gln     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Pro                                                                     
- (2) INFORMATION FOR SEQ ID NO:187:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 321 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:187:                           
- Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg As - #n Leu Gln Pro Cys Leu     
#                15                                                       
- Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pr - #o Ile Ile Ile Lys Ala     
#            30                                                           
- Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Th - #r Phe Tyr Leu Val Thr     
#        45                                                               
- Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gl - #y Ser Asn Cys Ser Ile     
#    60                                                                   
- Met Ile Asp Glu Ile Ile His His Leu Lys Ar - #g Pro Pro Ala Pro Leu     
#80                                                                       
- Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Va - #l Ser Ile Leu Met Asp     
#                95                                                       
- Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Ph - #e Val Arg Ala Val Lys     
#           110                                                           
- Asn Leu Glu Tyr Val Glu Gly Gly Gly Gly Se - #r Pro Gly Glu Pro Ser     
#       125                                                               
- Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pr - #o Ser Lys Glu Ser His     
#   140                                                                   
- Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Me - #t Pro Ala Phe Ala Ser     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Va - #l Ala Ser His Leu Gln     
#               175                                                       
- Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Ar - #g His Leu Ala Gln Pro     
#           190                                                           
- Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Le - #u Leu Lys Ser Leu Glu     
#       205                                                               
- Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Al - #a Leu Gln Glu Lys Leu     
#   220                                                                   
- Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Gl - #u Leu Val Leu Leu Gly     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- His Ser Leu Gly Ile Pro Trp Ala Pro Leu Se - #r Ser Cys Pro Ser Gln     
#               255                                                       
- Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Le - #u His Ser Gly Leu Phe     
#           270                                                           
- Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gl - #y Ile Ser Pro Glu Leu     
#       285                                                               
- Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Va - #l Ala Asp Phe Ala Thr     
#   300                                                                   
- Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Me - #t Ala Pro Ala Leu Gln     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Pro                                                                     
- (2) INFORMATION FOR SEQ ID NO:188:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 321 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:188:                           
- Ala Pro Ser Arg His Pro Ile Ile Ile Lys Al - #a Gly Asp Trp Gln Glu     
#                15                                                       
- Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Th - #r Leu Glu Gln Ala Gln     
#            30                                                           
- Glu Gln Gln Gly Gly Gly Ser Asn Cys Ser Il - #e Met Ile Asp Glu Ile     
#        45                                                               
- Ile His His Leu Lys Arg Pro Pro Ala Pro Le - #u Leu Asp Pro Asn Asn     
#    60                                                                   
- Leu Asn Asp Glu Asp Val Ser Ile Leu Met As - #p Arg Asn Leu Arg Leu     
#80                                                                       
- Pro Asn Leu Glu Ser Phe Val Arg Ala Val Ly - #s Asn Leu Glu Asn Ala     
#                95                                                       
- Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gl - #n Pro Cys Leu Pro Ser     
#           110                                                           
- Ala Thr Ala Tyr Val Glu Gly Gly Gly Gly Se - #r Pro Gly Glu Pro Ser     
#       125                                                               
- Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pr - #o Ser Lys Glu Ser His     
#   140                                                                   
- Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Me - #t Pro Ala Phe Ala Ser     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Va - #l Ala Ser His Leu Gln     
#               175                                                       
- Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Ar - #g His Leu Ala Gln Pro     
#           190                                                           
- Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Le - #u Leu Lys Ser Leu Glu     
#       205                                                               
- Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Al - #a Leu Gln Glu Lys Leu     
#   220                                                                   
- Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Gl - #u Leu Val Leu Leu Gly     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- His Ser Leu Gly Ile Pro Trp Ala Pro Leu Se - #r Ser Cys Pro Ser Gln     
#               255                                                       
- Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Le - #u His Ser Gly Leu Phe     
#           270                                                           
- Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gl - #y Ile Ser Pro Glu Leu     
#       285                                                               
- Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Va - #l Ala Asp Phe Ala Thr     
#   300                                                                   
- Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Me - #t Ala Pro Ala Leu Gln     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Pro                                                                     
- (2) INFORMATION FOR SEQ ID NO:189:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 321 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:189:                           
- Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Le - #u Thr Phe Tyr Leu Val     
#                15                                                       
- Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gl - #y Gly Ser Asn Cys Ser     
#            30                                                           
- Ile Met Ile Asp Glu Ile Ile His His Leu Ly - #s Arg Pro Pro Ala Pro     
#        45                                                               
- Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu As - #p Val Ser Ile Leu Met     
#    60                                                                   
- Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Se - #r Phe Val Arg Ala Val     
#80                                                                       
- Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Al - #a Ile Leu Arg Asn Leu     
#                95                                                       
- Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pr - #o Ser Arg His Pro Ile     
#           110                                                           
- Ile Ile Lys Tyr Val Glu Gly Gly Gly Gly Se - #r Pro Gly Glu Pro Ser     
#       125                                                               
- Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pr - #o Ser Lys Glu Ser His     
#   140                                                                   
- Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Me - #t Pro Ala Phe Ala Ser     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Va - #l Ala Ser His Leu Gln     
#               175                                                       
- Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Ar - #g His Leu Ala Gln Pro     
#           190                                                           
- Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Le - #u Leu Lys Ser Leu Glu     
#       205                                                               
- Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Al - #a Leu Gln Glu Lys Leu     
#   220                                                                   
- Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Gl - #u Leu Val Leu Leu Gly     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- His Ser Leu Gly Ile Pro Trp Ala Pro Leu Se - #r Ser Cys Pro Ser Gln     
#               255                                                       
- Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Le - #u His Ser Gly Leu Phe     
#           270                                                           
- Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gl - #y Ile Ser Pro Glu Leu     
#       285                                                               
- Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Va - #l Ala Asp Phe Ala Thr     
#   300                                                                   
- Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Me - #t Ala Pro Ala Leu Gln     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Pro                                                                     
- (2) INFORMATION FOR SEQ ID NO:190:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 329 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:190:                           
- Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Va - #l Ser Ile Leu Met Asp     
#                15                                                       
- Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Ph - #e Val Arg Ala Val Lys     
#            30                                                           
- Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Il - #e Leu Arg Asn Leu Gln     
#        45                                                               
- Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Se - #r Arg His Pro Ile Ile     
#    60                                                                   
- Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Gl - #u Lys Leu Thr Phe Tyr     
#80                                                                       
- Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gl - #n Gly Gly Gly Ser Gly     
#                95                                                       
- Gly Gly Ser Gly Gly Gly Ser Asn Cys Ser Il - #e Met Ile Asp Glu Ile     
#           110                                                           
- Ile His His Leu Lys Arg Pro Pro Ala Pro Le - #u Tyr Val Glu Gly Gly     
#       125                                                               
- Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Il - #e Ser Thr Ile Asn Pro     
#   140                                                                   
- Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pr - #o Asn Met Ala Thr Gln     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gl - #n Arg Arg Ala Gly Gly     
#               175                                                       
- Val Leu Val Ala Ser His Leu Gln Ser Phe Le - #u Glu Val Ser Tyr Arg     
#           190                                                           
- Val Leu Arg His Leu Ala Gln Pro Ser Gly Gl - #y Ser Gly Gly Ser Gln     
#       205                                                               
- Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Ar - #g Lys Ile Gln Gly Asp     
#   220                                                                   
- Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Th - #r Tyr Lys Leu Cys His     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Pro Glu Glu Leu Val Leu Leu Gly His Ser Le - #u Gly Ile Pro Trp Ala     
#               255                                                       
- Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gl - #n Leu Ala Gly Cys Leu     
#           270                                                           
- Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gl - #n Gly Leu Leu Gln Ala     
#       285                                                               
- Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Th - #r Leu Asp Thr Leu Gln     
#   300                                                                   
- Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Tr - #p Gln Gln Met Glu Glu     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Leu Gly Met Ala Pro Ala Leu Gln Pro                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:191:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 329 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:191:                           
- Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg As - #n Leu Gln Pro Cys Leu     
#                15                                                       
- Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pr - #o Ile Ile Ile Lys Ala     
#            30                                                           
- Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Th - #r Phe Tyr Leu Val Thr     
#        45                                                               
- Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gl - #y Ser Gly Gly Gly Ser     
#    60                                                                   
- Gly Gly Gly Ser Asn Cys Ser Ile Met Ile As - #p Glu Ile Ile His His     
#80                                                                       
- Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pr - #o Asn Asn Leu Asn Asp     
#                95                                                       
- Glu Asp Val Ser Ile Leu Met Asp Arg Asn Le - #u Arg Leu Pro Asn Leu     
#           110                                                           
- Glu Ser Phe Val Arg Ala Val Lys Asn Leu Gl - #u Tyr Val Glu Gly Gly     
#       125                                                               
- Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Il - #e Ser Thr Ile Asn Pro     
#   140                                                                   
- Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pr - #o Asn Met Ala Thr Gln     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gl - #n Arg Arg Ala Gly Gly     
#               175                                                       
- Val Leu Val Ala Ser His Leu Gln Ser Phe Le - #u Glu Val Ser Tyr Arg     
#           190                                                           
- Val Leu Arg His Leu Ala Gln Pro Ser Gly Gl - #y Ser Gly Gly Ser Gln     
#       205                                                               
- Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Ar - #g Lys Ile Gln Gly Asp     
#   220                                                                   
- Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Th - #r Tyr Lys Leu Cys His     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Pro Glu Glu Leu Val Leu Leu Gly His Ser Le - #u Gly Ile Pro Trp Ala     
#               255                                                       
- Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gl - #n Leu Ala Gly Cys Leu     
#           270                                                           
- Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gl - #n Gly Leu Leu Gln Ala     
#       285                                                               
- Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Th - #r Leu Asp Thr Leu Gln     
#   300                                                                   
- Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Tr - #p Gln Gln Met Glu Glu     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Leu Gly Met Ala Pro Ala Leu Gln Pro                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:192:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 329 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:192:                           
- Ala Pro Ser Arg His Pro Ile Ile Ile Lys Al - #a Gly Asp Trp Gln Glu     
#                15                                                       
- Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Th - #r Leu Glu Gln Ala Gln     
#            30                                                           
- Glu Gln Gln Gly Gly Gly Ser Gly Gly Gly Se - #r Gly Gly Gly Ser Asn     
#        45                                                               
- Cys Ser Ile Met Ile Asp Glu Ile Ile His Hi - #s Leu Lys Arg Pro Pro     
#    60                                                                   
- Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn As - #p Glu Asp Val Ser Ile     
#80                                                                       
- Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Le - #u Glu Ser Phe Val Arg     
#                95                                                       
- Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Il - #e Glu Ala Ile Leu Arg     
#           110                                                           
- Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Al - #a Tyr Val Glu Gly Gly     
#       125                                                               
- Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Il - #e Ser Thr Ile Asn Pro     
#   140                                                                   
- Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pr - #o Asn Met Ala Thr Gln     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gl - #n Arg Arg Ala Gly Gly     
#               175                                                       
- Val Leu Val Ala Ser His Leu Gln Ser Phe Le - #u Glu Val Ser Tyr Arg     
#           190                                                           
- Val Leu Arg His Leu Ala Gln Pro Ser Gly Gl - #y Ser Gly Gly Ser Gln     
#       205                                                               
- Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Ar - #g Lys Ile Gln Gly Asp     
#   220                                                                   
- Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Th - #r Tyr Lys Leu Cys His     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Pro Glu Glu Leu Val Leu Leu Gly His Ser Le - #u Gly Ile Pro Trp Ala     
#               255                                                       
- Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gl - #n Leu Ala Gly Cys Leu     
#           270                                                           
- Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gl - #n Gly Leu Leu Gln Ala     
#       285                                                               
- Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Th - #r Leu Asp Thr Leu Gln     
#   300                                                                   
- Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Tr - #p Gln Gln Met Glu Glu     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Leu Gly Met Ala Pro Ala Leu Gln Pro                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:193:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 299 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:193:                           
- Gly Gly Ser Gly Gly Gly Ser Asn Cys Ser Il - #e Met Ile Asp Glu Ile     
#                15                                                       
- Ile His His Leu Lys Arg Pro Pro Ala Pro Le - #u Leu Asp Pro Asn Asn     
#            30                                                           
- Leu Asn Asp Glu Asp Val Ser Ile Leu Met As - #p Arg Asn Leu Arg Leu     
#        45                                                               
- Pro Asn Leu Glu Ser Phe Val Arg Ala Val Ly - #s Asn Leu Glu Asn Ala     
#    60                                                                   
- Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gl - #n Pro Cys Leu Pro Ser     
#80                                                                       
- Ala Thr Ala Ala Pro Ser Arg His Pro Ile Il - #e Ile Lys Tyr Val Glu     
#                95                                                       
- Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gl - #y Pro Ile Ser Thr Ile     
#           110                                                           
- Asn Pro Ser Pro Pro Ser Lys Glu Ser His Ly - #s Ser Pro Asn Met Ala     
#       125                                                               
- Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Al - #a Phe Gln Arg Arg Ala     
#   140                                                                   
- Gly Gly Val Leu Val Ala Ser His Leu Gln Se - #r Phe Leu Glu Val Ser     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Tyr Arg Val Leu Arg His Leu Ala Gln Pro Se - #r Gly Gly Ser Gly Gly     
#               175                                                       
- Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gl - #n Val Arg Lys Ile Gln     
#           190                                                           
- Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cy - #s Ala Thr Tyr Lys Leu     
#       205                                                               
- Cys His Pro Glu Glu Leu Val Leu Leu Gly Hi - #s Ser Leu Gly Ile Pro     
#   220                                                                   
- Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Al - #a Leu Gln Leu Ala Gly     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Cys Leu Ser Gln Leu His Ser Gly Leu Phe Le - #u Tyr Gln Gly Leu Leu     
#               255                                                       
- Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gl - #y Pro Thr Leu Asp Thr     
#           270                                                           
- Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Th - #r Ile Trp Gln Gln Met     
#       285                                                               
- Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pr - #o                         
#   295                                                                   
- (2) INFORMATION FOR SEQ ID NO:194:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 329 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:194:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Tyr Lys Leu Cys His Pro Gl - #u Glu Leu Val Leu Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gly His Ser Leu Gly Ile Pro Trp Ala Pro Le - #u Ser Ser Cys Pro Ser     
#               175                                                       
- Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gl - #n Leu His Ser Gly Leu     
#           190                                                           
- Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Gl - #u Gly Ile Ser Pro Glu     
#       205                                                               
- Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu As - #p Val Ala Asp Phe Ala     
#   220                                                                   
- Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gl - #y Met Ala Pro Ala Leu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Al - #a Ser Ala Phe Gln Arg     
#               255                                                       
- Arg Ala Gly Gly Val Leu Val Ala Ser His Le - #u Gln Ser Phe Leu Glu     
#           270                                                           
- Val Ser Tyr Arg Val Leu Arg His Leu Ala Gl - #n Pro Gly Gly Gly Ser     
#       285                                                               
- Asp Met Ala Thr Pro Leu Gly Pro Ala Ser Se - #r Leu Pro Gln Ser Phe     
#   300                                                                   
- Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Il - #e Gln Gly Asp Gly Ala     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Ala Leu Gln Glu Lys Leu Cys Ala Thr                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:195:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 329 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:195:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Pro Glu Leu Gly Pro Thr Le - #u Asp Thr Leu Gln Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gl - #n Gln Met Glu Glu Leu     
#               175                                                       
- Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gl - #y Ala Met Pro Ala Phe     
#           190                                                           
- Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Va - #l Leu Val Ala Ser His     
#       205                                                               
- Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Va - #l Leu Arg His Leu Ala     
#   220                                                                   
- Gln Pro Gly Gly Gly Ser Asp Met Ala Thr Pr - #o Leu Gly Pro Ala Ser     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Le - #u Glu Gln Val Arg Lys     
#               255                                                       
- Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Ly - #s Leu Cys Ala Thr Tyr     
#           270                                                           
- Lys Leu Cys His Pro Glu Glu Leu Val Leu Le - #u Gly His Ser Leu Gly     
#       285                                                               
- Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Se - #r Gln Ala Leu Gln Leu     
#   300                                                                   
- Ala Gly Cys Leu Ser Gln Leu His Ser Gly Le - #u Phe Leu Tyr Gln Gly     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Leu Leu Gln Ala Leu Glu Gly Ile Ser                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:196:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 329 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:196:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Ser Ala Phe Gln Arg Arg Al - #a Gly Gly Val Leu Val     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ala Ser His Leu Gln Ser Phe Leu Glu Val Se - #r Tyr Arg Val Leu Arg     
#               175                                                       
- His Leu Ala Gln Pro Gly Gly Gly Ser Asp Me - #t Ala Thr Pro Leu Gly     
#           190                                                           
- Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Le - #u Lys Ser Leu Glu Gln     
#       205                                                               
- Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Le - #u Gln Glu Lys Leu Cys     
#   220                                                                   
- Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Le - #u Val Leu Leu Gly His     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Se - #r Cys Pro Ser Gln Ala     
#               255                                                       
- Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu Hi - #s Ser Gly Leu Phe Leu     
#           270                                                           
- Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Il - #e Ser Pro Glu Leu Gly     
#       285                                                               
- Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Al - #a Asp Phe Ala Thr Thr     
#   300                                                                   
- Ile Trp Gln Gln Met Glu Glu Leu Gly Met Al - #a Pro Ala Leu Gln Pro     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Thr Gln Gly Ala Met Pro Ala Phe Ala                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:197:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 329 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:197:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Met Ala Pro Ala Leu Gln Pr - #o Thr Gln Gly Ala Met     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Al - #a Gly Gly Val Leu Val     
#               175                                                       
- Ala Ser His Leu Gln Ser Phe Leu Glu Val Se - #r Tyr Arg Val Leu Arg     
#           190                                                           
- His Leu Ala Gln Pro Gly Gly Gly Ser Asp Me - #t Ala Thr Pro Leu Gly     
#       205                                                               
- Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Le - #u Lys Ser Leu Glu Gln     
#   220                                                                   
- Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Le - #u Gln Glu Lys Leu Cys     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Le - #u Val Leu Leu Gly His     
#               255                                                       
- Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Se - #r Cys Pro Ser Gln Ala     
#           270                                                           
- Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu Hi - #s Ser Gly Leu Phe Leu     
#       285                                                               
- Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Il - #e Ser Pro Glu Leu Gly     
#   300                                                                   
- Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Al - #a Asp Phe Ala Thr Thr     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Ile Trp Gln Gln Met Glu Glu Leu Gly                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:198:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 329 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:198:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Thr Gln Gly Ala Met Pro Al - #a Phe Ala Ser Ala Phe     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gln Arg Arg Ala Gly Gly Val Leu Val Ala Se - #r His Leu Gln Ser Phe     
#               175                                                       
- Leu Glu Val Ser Tyr Arg Val Leu Arg His Le - #u Ala Gln Pro Gly Gly     
#           190                                                           
- Gly Ser Asp Met Ala Thr Pro Leu Gly Pro Al - #a Ser Ser Leu Pro Gln     
#       205                                                               
- Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Ar - #g Lys Ile Gln Gly Asp     
#   220                                                                   
- Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Th - #r Tyr Lys Leu Cys His     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Pro Glu Glu Leu Val Leu Leu Gly His Ser Le - #u Gly Ile Pro Trp Ala     
#               255                                                       
- Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gl - #n Leu Ala Gly Cys Leu     
#           270                                                           
- Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gl - #n Gly Leu Leu Gln Ala     
#       285                                                               
- Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Th - #r Leu Asp Thr Leu Gln     
#   300                                                                   
- Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Tr - #p Gln Gln Met Glu Glu     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Leu Gly Met Ala Pro Ala Leu Gln Pro                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:199:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 319 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:199:                           
- Met Ala Asn Cys Ser Asn Met Ile Asp Glu Il - #e Ile Thr His Leu Lys     
#                15                                                       
- Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn As - #n Leu Asn Gly Glu Asp     
#            30                                                           
- Gln Asp Ile Leu Met Asp Asn Asn Leu Arg Ar - #g Pro Asn Leu Glu Ala     
#        45                                                               
- Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Al - #a Ser Ala Ile Glu Ser     
#    60                                                                   
- Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Le - #u Ala Thr Ala Ala Pro     
#80                                                                       
- Thr Arg His Pro Ile His Ile Lys Asp Gly As - #p Trp Asn Glu Phe Arg     
#                95                                                       
- Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Gl - #u Asn Ala Gln Ala Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Thr Gln Gly Ala Met Pro Al - #a Phe Ala Ser Ala Phe     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gln Arg Arg Ala Gly Gly Val Leu Val Ala Se - #r His Leu Gln Ser Phe     
#               175                                                       
- Leu Glu Val Ser Tyr Arg Val Leu Arg His Le - #u Ala Gln Pro Ser Gly     
#           190                                                           
- Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Ly - #s Ser Leu Glu Gln Val     
#       205                                                               
- Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gl - #n Glu Lys Leu Cys Ala     
#   220                                                                   
- Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Va - #l Leu Leu Gly His Ser     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cy - #s Pro Ser Gln Ala Leu     
#               255                                                       
- Gln Leu Ala Gly Cys Leu Ser Gln Leu His Se - #r Gly Leu Phe Leu Tyr     
#           270                                                           
- Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Se - #r Pro Glu Leu Gly Pro     
#       285                                                               
- Thr Leu Asp Thr Leu Gln Leu Asp Val Ala As - #p Phe Ala Thr Thr Ile     
#   300                                                                   
- Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pr - #o Ala Leu Gln Pro         
305                 3 - #10                 3 - #15                       
- (2) INFORMATION FOR SEQ ID NO:200:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 322 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:200:                           
- Met Ala Asn Cys Ser Asn Met Ile Asp Glu Il - #e Ile Thr His Leu Lys     
#                15                                                       
- Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn As - #n Leu Asn Gly Glu Asp     
#            30                                                           
- Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Ar - #g Pro Asn Leu Glu Ala     
#        45                                                               
- Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Al - #a Ser Ala Ile Glu Ser     
#    60                                                                   
- Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Le - #u Ala Thr Ala Ala Pro     
#80                                                                       
- Thr Arg His Pro Ile Ile Ile Arg Asp Gly As - #p Trp Asn Glu Phe Arg     
#                95                                                       
- Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Gl - #u Asn Ala Gln Ala Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Thr Gln Gly Ala Met Pro Al - #a Phe Ala Ser Ala Phe     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gln Arg Arg Ala Gly Gly Val Leu Val Ala Se - #r His Leu Gln Ser Phe     
#               175                                                       
- Leu Glu Val Ser Tyr Arg Val Leu Arg His Le - #u Ala Gln Pro Thr Pro     
#           190                                                           
- Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Ph - #e Leu Leu Lys Ser Leu     
#       205                                                               
- Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Al - #a Ala Leu Gln Glu Lys     
#   220                                                                   
- Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Gl - #u Glu Leu Val Leu Leu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Gly His Ser Leu Gly Ile Pro Trp Ala Pro Le - #u Ser Ser Cys Pro Ser     
#               255                                                       
- Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gl - #n Leu His Ser Gly Leu     
#           270                                                           
- Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Gl - #u Gly Ile Ser Pro Glu     
#       285                                                               
- Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu As - #p Val Ala Asp Phe Ala     
#   300                                                                   
- Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gl - #y Met Ala Pro Ala Leu     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Gln Pro                                                                 
- (2) INFORMATION FOR SEQ ID NO:201:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 319 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:201:                           
- Met Ala Asn Cys Ser Asn Met Ile Asp Glu Il - #e Ile Thr His Leu Lys     
#                15                                                       
- Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn As - #n Leu Asn Gly Glu Asp     
#            30                                                           
- Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Ar - #g Pro Asn Leu Glu Ala     
#        45                                                               
- Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Al - #a Ser Ala Ile Glu Ser     
#    60                                                                   
- Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Le - #u Ala Thr Ala Ala Pro     
#80                                                                       
- Thr Arg His Pro Ile Ile Ile Arg Asp Gly As - #p Trp Asn Glu Phe Arg     
#                95                                                       
- Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Gl - #u Asn Ala Gln Ala Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Thr Gln Gly Ala Met Pro Al - #a Phe Ala Ser Ala Phe     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gln Arg Arg Ala Gly Gly Val Leu Val Ala Se - #r His Leu Gln Ser Phe     
#               175                                                       
- Leu Glu Val Ser Tyr Arg Val Leu Arg His Le - #u Ala Gln Pro Ser Gly     
#           190                                                           
- Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Ly - #s Ser Leu Glu Gln Val     
#       205                                                               
- Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gl - #n Glu Lys Leu Cys Ala     
#   220                                                                   
- Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Va - #l Leu Leu Gly His Ser     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cy - #s Pro Ser Gln Ala Leu     
#               255                                                       
- Gln Leu Ala Gly Cys Leu Ser Gln Leu His Se - #r Gly Leu Phe Leu Tyr     
#           270                                                           
- Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Se - #r Pro Glu Leu Gly Pro     
#       285                                                               
- Thr Leu Asp Thr Leu Gln Leu Asp Val Ala As - #p Phe Ala Thr Thr Ile     
#   300                                                                   
- Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pr - #o Ala Leu Gln Pro         
305                 3 - #10                 3 - #15                       
- (2) INFORMATION FOR SEQ ID NO:202:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 322 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:202:                           
- Met Ala Asn Cys Ser Asn Met Ile Asp Glu Il - #e Ile Thr His Leu Lys     
#                15                                                       
- Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn As - #n Leu Asn Gly Glu Asp     
#            30                                                           
- Gln Asp Ile Leu Met Asp Asn Asn Leu Arg Ar - #g Pro Asn Leu Glu Ala     
#        45                                                               
- Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Al - #a Ser Ala Ile Glu Ser     
#    60                                                                   
- Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Le - #u Ala Thr Ala Ala Pro     
#80                                                                       
- Thr Arg His Pro Ile His Ile Lys Asp Gly As - #p Trp Asn Glu Phe Arg     
#                95                                                       
- Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Gl - #u Asn Ala Gln Ala Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Thr Gln Gly Ala Met Pro Al - #a Phe Ala Ser Ala Phe     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gln Arg Arg Ala Gly Gly Val Leu Val Ala Se - #r His Leu Gln Ser Phe     
#               175                                                       
- Leu Glu Val Ser Tyr Arg Val Leu Arg His Le - #u Ala Gln Pro Thr Pro     
#           190                                                           
- Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Ph - #e Leu Leu Lys Ser Leu     
#       205                                                               
- Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Al - #a Ala Leu Gln Glu Lys     
#   220                                                                   
- Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Gl - #u Glu Leu Val Leu Leu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Gly His Ser Leu Gly Ile Pro Trp Ala Pro Le - #u Ser Ser Cys Pro Ser     
#               255                                                       
- Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gl - #n Leu His Ser Gly Leu     
#           270                                                           
- Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Gl - #u Gly Ile Ser Pro Glu     
#       285                                                               
- Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu As - #p Val Ala Asp Phe Ala     
#   300                                                                   
- Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gl - #y Met Ala Pro Ala Leu     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Gln Pro                                                                 
- (2) INFORMATION FOR SEQ ID NO:203:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 306 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:203:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Glu Val His Pro Leu Pro Thr Pro Va - #l Leu Leu Pro Ala Val     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Me - #t Glu Glu Thr Lys Ala     
#               175                                                       
- Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Le - #u Glu Gly Val Met Ala     
#           190                                                           
- Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Se - #r Ser Leu Leu Gly Gln     
#       205                                                               
- Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Al - #a Leu Gln Ser Leu Leu     
#   220                                                                   
- Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Th - #r Ala His Lys Asp Pro     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Asn Ala Ile Phe Leu Ser Phe Gln His Leu Le - #u Arg Gly Lys Val Arg     
#               255                                                       
- Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cy - #s Val Arg Glu Phe Gly     
#           270                                                           
- Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cy - #s Asp Leu Arg Val Leu     
#       285                                                               
- Ser Lys Leu Leu Arg Asp Ser His Val Leu Hi - #s Ser Arg Leu Ser Gln     
#   300                                                                   
- Cys Pro                                                                 
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:204:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 306 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:204:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#               175                                                       
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#           190                                                           
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#       205                                                               
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Leu     
#   220                                                                   
- Pro Pro Gln Gly Arg Thr Thr Ala His Lys As - #p Pro Asn Ala Ile Phe     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Ser Phe Gln His Leu Leu Arg Gly Lys Va - #l Arg Phe Leu Met Leu     
#               255                                                       
- Val Gly Gly Ser Thr Leu Cys Val Arg Glu Ph - #e Gly Gly Asn Met Ala     
#           270                                                           
- Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Va - #l Leu Ser Lys Leu Leu     
#       285                                                               
- Arg Asp Ser His Val Leu His Ser Arg Leu Se - #r Gln Cys Pro Glu Val     
#   300                                                                   
- His Pro                                                                 
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:205:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 306 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:205:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Val Leu Leu Pro Ala Val Asp Phe Se - #r Leu Gly Glu Trp Lys     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Il - #e Leu Gly Ala Val Thr     
#               175                                                       
- Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gl - #y Gln Leu Gly Pro Thr     
#           190                                                           
- Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gl - #y Gln Val Arg Leu Leu     
#       205                                                               
- Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gl - #n Leu Pro Pro Gln Gly     
#   220                                                                   
- Arg Thr Thr Ala His Lys Asp Pro Asn Ala Il - #e Phe Leu Ser Phe Gln     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- His Leu Leu Arg Gly Lys Val Arg Phe Leu Me - #t Leu Val Gly Gly Ser     
#               255                                                       
- Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Me - #t Ala Ser Pro Ala Pro     
#           270                                                           
- Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Le - #u Leu Arg Asp Ser His     
#       285                                                               
- Val Leu His Ser Arg Leu Ser Gln Cys Pro Gl - #u Val His Pro Leu Pro     
#   300                                                                   
- Thr Pro                                                                 
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:206:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 306 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:206:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Ala Val Asp Phe Ser Leu Gly Glu Tr - #p Lys Thr Gln Met Glu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Va - #l Thr Leu Leu Leu Glu     
#               175                                                       
- Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pr - #o Thr Cys Leu Ser Ser     
#           190                                                           
- Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Le - #u Leu Leu Gly Ala Leu     
#       205                                                               
- Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gl - #n Gly Arg Thr Thr Ala     
#   220                                                                   
- His Lys Asp Pro Asn Ala Ile Phe Leu Ser Ph - #e Gln His Leu Leu Arg     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Gly Lys Val Arg Phe Leu Met Leu Val Gly Gl - #y Ser Thr Leu Cys Val     
#               255                                                       
- Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Al - #a Pro Pro Ala Cys Asp     
#           270                                                           
- Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Se - #r His Val Leu His Ser     
#       285                                                               
- Arg Leu Ser Gln Cys Pro Glu Val His Pro Le - #u Pro Thr Pro Val Leu     
#   300                                                                   
- Leu Pro                                                                 
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:207:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 306 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:207:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Asp Phe Ser Leu Gly Glu Trp Lys Th - #r Gln Met Glu Glu Thr     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Le - #u Leu Leu Glu Gly Val     
#               175                                                       
- Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cy - #s Leu Ser Ser Leu Leu     
#           190                                                           
- Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Le - #u Gly Ala Leu Gln Ser     
#       205                                                               
- Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Ar - #g Thr Thr Ala His Lys     
#   220                                                                   
- Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln Hi - #s Leu Leu Arg Gly Lys     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Val Arg Phe Leu Met Leu Val Gly Gly Ser Th - #r Leu Cys Val Arg Glu     
#               255                                                       
- Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pr - #o Ala Cys Asp Leu Arg     
#           270                                                           
- Val Leu Ser Lys Leu Leu Arg Asp Ser His Va - #l Leu His Ser Arg Leu     
#       285                                                               
- Ser Gln Cys Pro Glu Val His Pro Leu Pro Th - #r Pro Val Leu Leu Pro     
#   300                                                                   
- Ala Val                                                                 
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:208:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 306 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:208:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Gly Glu Trp Lys Thr Gln Met Glu Gl - #u Thr Lys Ala Gln Asp     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gl - #y Val Met Ala Ala Arg     
#               175                                                       
- Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Le - #u Leu Gly Gln Leu Ser     
#           190                                                           
- Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gl - #n Ser Leu Leu Gly Thr     
#       205                                                               
- Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala Hi - #s Lys Asp Pro Asn Ala     
#   220                                                                   
- Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gl - #y Lys Val Arg Phe Leu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Met Leu Val Gly Gly Ser Thr Leu Cys Val Ar - #g Glu Phe Gly Gly Asn     
#               255                                                       
- Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Le - #u Arg Val Leu Ser Lys     
#           270                                                           
- Leu Leu Arg Asp Ser His Val Leu His Ser Ar - #g Leu Ser Gln Cys Pro     
#       285                                                               
- Glu Val His Pro Leu Pro Thr Pro Val Leu Le - #u Pro Ala Val Asp Phe     
#   300                                                                   
- Ser Leu                                                                 
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:209:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 306 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:209:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Gly Pro Thr Cys Leu Ser Ser Leu Le - #u Gly Gln Leu Ser Gly     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Se - #r Leu Leu Gly Thr Gln     
#               175                                                       
- Leu Pro Pro Gln Gly Arg Thr Thr Ala His Ly - #s Asp Pro Asn Ala Ile     
#           190                                                           
- Phe Leu Ser Phe Gln His Leu Leu Arg Gly Ly - #s Val Arg Phe Leu Met     
#       205                                                               
- Leu Val Gly Gly Ser Thr Leu Cys Val Arg Gl - #u Phe Gly Gly Asn Met     
#   220                                                                   
- Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Ar - #g Val Leu Ser Lys Leu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Arg Asp Ser His Val Leu His Ser Arg Le - #u Ser Gln Cys Pro Glu     
#               255                                                       
- Val His Pro Leu Pro Thr Pro Val Leu Leu Pr - #o Ala Val Asp Phe Ser     
#           270                                                           
- Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Th - #r Lys Ala Gln Asp Ile     
#       285                                                               
- Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Va - #l Met Ala Ala Arg Gly     
#   300                                                                   
- Gln Leu                                                                 
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:210:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 306 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:210:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Gly Thr Gln Leu Pro Pro Gln Gly Ar - #g Thr Thr Ala His Lys     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln Hi - #s Leu Leu Arg Gly Lys     
#               175                                                       
- Val Arg Phe Leu Met Leu Val Gly Gly Ser Th - #r Leu Cys Val Arg Glu     
#           190                                                           
- Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pr - #o Ala Cys Asp Leu Arg     
#       205                                                               
- Val Leu Ser Lys Leu Leu Arg Asp Ser His Va - #l Leu His Ser Arg Leu     
#   220                                                                   
- Ser Gln Cys Pro Glu Val His Pro Leu Pro Th - #r Pro Val Leu Leu Pro     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Th - #r Gln Met Glu Glu Thr     
#               255                                                       
- Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Le - #u Leu Leu Glu Gly Val     
#           270                                                           
- Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cy - #s Leu Ser Ser Leu Leu     
#       285                                                               
- Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Le - #u Gly Ala Leu Gln Ser     
#   300                                                                   
- Leu Leu                                                                 
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:211:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 306 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:211:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Gly Arg Thr Thr Ala His Lys Asp Pr - #o Asn Ala Ile Phe Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ser Phe Gln His Leu Leu Arg Gly Lys Val Ar - #g Phe Leu Met Leu Val     
#               175                                                       
- Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gl - #y Gly Asn Met Ala Ser     
#           190                                                           
- Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Le - #u Ser Lys Leu Leu Arg     
#       205                                                               
- Asp Ser His Val Leu His Ser Arg Leu Ser Gl - #n Cys Pro Glu Val His     
#   220                                                                   
- Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Va - #l Asp Phe Ser Leu Gly     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Al - #a Gln Asp Ile Leu Gly     
#               255                                                       
- Ala Val Thr Leu Leu Leu Glu Gly Val Met Al - #a Ala Arg Gly Gln Leu     
#           270                                                           
- Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gl - #n Leu Ser Gly Gln Val     
#       285                                                               
- Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Le - #u Gly Thr Gln Leu Pro     
#   300                                                                   
- Pro Gln                                                                 
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:212:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 306 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:212:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Ala His Lys Asp Pro Asn Ala Ile Ph - #e Leu Ser Phe Gln His     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Leu Leu Arg Gly Lys Val Arg Phe Leu Met Le - #u Val Gly Gly Ser Thr     
#               175                                                       
- Leu Cys Val Arg Glu Phe Gly Gly Asn Met Al - #a Ser Pro Ala Pro Pro     
#           190                                                           
- Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Le - #u Arg Asp Ser His Val     
#       205                                                               
- Leu His Ser Arg Leu Ser Gln Cys Pro Glu Va - #l His Pro Leu Pro Thr     
#   220                                                                   
- Pro Val Leu Leu Pro Ala Val Asp Phe Ser Le - #u Gly Glu Trp Lys Thr     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Le - #u Gly Ala Val Thr Leu     
#               255                                                       
- Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gl - #n Leu Gly Pro Thr Cys     
#           270                                                           
- Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gl - #n Val Arg Leu Leu Leu     
#       285                                                               
- Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Le - #u Pro Pro Gln Gly Arg     
#   300                                                                   
- Thr Thr                                                                 
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:213:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 306 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:213:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Asp Pro Asn Ala Ile Phe Leu Ser Ph - #e Gln His Leu Leu Arg     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gly Lys Val Arg Phe Leu Met Leu Val Gly Gl - #y Ser Thr Leu Cys Val     
#               175                                                       
- Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Al - #a Pro Pro Ala Cys Asp     
#           190                                                           
- Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Se - #r His Val Leu His Ser     
#       205                                                               
- Arg Leu Ser Gln Cys Pro Glu Val His Pro Le - #u Pro Thr Pro Val Leu     
#   220                                                                   
- Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Tr - #p Lys Thr Gln Met Glu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Va - #l Thr Leu Leu Leu Glu     
#               255                                                       
- Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pr - #o Thr Cys Leu Ser Ser     
#           270                                                           
- Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Le - #u Leu Leu Gly Ala Leu     
#       285                                                               
- Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gl - #n Gly Arg Thr Thr Ala     
#   300                                                                   
- His Lys                                                                 
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:214:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 306 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:214:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Ala Ile Phe Leu Ser Phe Gln His Le - #u Leu Arg Gly Lys Val     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Arg Phe Leu Met Leu Val Gly Gly Ser Thr Le - #u Cys Val Arg Glu Phe     
#               175                                                       
- Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Al - #a Cys Asp Leu Arg Val     
#           190                                                           
- Leu Ser Lys Leu Leu Arg Asp Ser His Val Le - #u His Ser Arg Leu Ser     
#       205                                                               
- Gln Cys Pro Glu Val His Pro Leu Pro Thr Pr - #o Val Leu Leu Pro Ala     
#   220                                                                   
- Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gl - #n Met Glu Glu Thr Lys     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Le - #u Leu Glu Gly Val Met     
#               255                                                       
- Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Le - #u Ser Ser Leu Leu Gly     
#           270                                                           
- Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gl - #y Ala Leu Gln Ser Leu     
#       285                                                               
- Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Th - #r Thr Ala His Lys Asp     
#   300                                                                   
- Pro Asn                                                                 
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:215:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:215:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Glu Val His Pro Leu Pro Thr Pro Va - #l Leu Leu Pro Ala Val     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Me - #t Glu Glu Thr Lys Ala     
#               175                                                       
- Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Le - #u Glu Gly Val Met Ala     
#           190                                                           
- Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Se - #r Ser Leu Leu Gly Gln     
#       205                                                               
- Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Al - #a Leu Gln Ser Leu Leu     
#   220                                                                   
- Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Th - #r Ala His Lys Asp Pro     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Asn Ala Ile Phe Leu Ser Phe Gln His Leu Le - #u Arg Gly Lys Val Arg     
#               255                                                       
- Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cy - #s Val Arg Glu Phe Gly     
#           270                                                           
- Asn Met Ala Ser Pro Ala Pro Pro Ala Cys As - #p Leu Arg Val Leu Ser     
#       285                                                               
- Lys Leu Leu Arg Asp Ser His Val Leu His Se - #r Arg Leu Ser Gln Cys     
#   300                                                                   
- Pro                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:216:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:216:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#               175                                                       
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#           190                                                           
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#       205                                                               
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Leu     
#   220                                                                   
- Pro Pro Gln Gly Arg Thr Thr Ala His Lys As - #p Pro Asn Ala Ile Phe     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Ser Phe Gln His Leu Leu Arg Gly Lys Va - #l Arg Phe Leu Met Leu     
#               255                                                       
- Val Gly Gly Ser Thr Leu Cys Val Arg Glu Ph - #e Gly Asn Met Ala Ser     
#           270                                                           
- Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Le - #u Ser Lys Leu Leu Arg     
#       285                                                               
- Asp Ser His Val Leu His Ser Arg Leu Ser Gl - #n Cys Pro Glu Val His     
#   300                                                                   
- Pro                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:217:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:217:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Val Leu Leu Pro Ala Val Asp Phe Se - #r Leu Gly Glu Trp Lys     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Il - #e Leu Gly Ala Val Thr     
#               175                                                       
- Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gl - #y Gln Leu Gly Pro Thr     
#           190                                                           
- Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gl - #y Gln Val Arg Leu Leu     
#       205                                                               
- Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gl - #n Leu Pro Pro Gln Gly     
#   220                                                                   
- Arg Thr Thr Ala His Lys Asp Pro Asn Ala Il - #e Phe Leu Ser Phe Gln     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- His Leu Leu Arg Gly Lys Val Arg Phe Leu Me - #t Leu Val Gly Gly Ser     
#               255                                                       
- Thr Leu Cys Val Arg Glu Phe Gly Asn Met Al - #a Ser Pro Ala Pro Pro     
#           270                                                           
- Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Le - #u Arg Asp Ser His Val     
#       285                                                               
- Leu His Ser Arg Leu Ser Gln Cys Pro Glu Va - #l His Pro Leu Pro Thr     
#   300                                                                   
- Pro                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:218:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:218:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Ala Val Asp Phe Ser Leu Gly Glu Tr - #p Lys Thr Gln Met Glu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Va - #l Thr Leu Leu Leu Glu     
#               175                                                       
- Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pr - #o Thr Cys Leu Ser Ser     
#           190                                                           
- Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Le - #u Leu Leu Gly Ala Leu     
#       205                                                               
- Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gl - #n Gly Arg Thr Thr Ala     
#   220                                                                   
- His Lys Asp Pro Asn Ala Ile Phe Leu Ser Ph - #e Gln His Leu Leu Arg     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Gly Lys Val Arg Phe Leu Met Leu Val Gly Gl - #y Ser Thr Leu Cys Val     
#               255                                                       
- Arg Glu Phe Gly Asn Met Ala Ser Pro Ala Pr - #o Pro Ala Cys Asp Leu     
#           270                                                           
- Arg Val Leu Ser Lys Leu Leu Arg Asp Ser Hi - #s Val Leu His Ser Arg     
#       285                                                               
- Leu Ser Gln Cys Pro Glu Val His Pro Leu Pr - #o Thr Pro Val Leu Leu     
#   300                                                                   
- Pro                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:219:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:219:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Asp Phe Ser Leu Gly Glu Trp Lys Th - #r Gln Met Glu Glu Thr     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Le - #u Leu Leu Glu Gly Val     
#               175                                                       
- Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cy - #s Leu Ser Ser Leu Leu     
#           190                                                           
- Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Le - #u Gly Ala Leu Gln Ser     
#       205                                                               
- Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Ar - #g Thr Thr Ala His Lys     
#   220                                                                   
- Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln Hi - #s Leu Leu Arg Gly Lys     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Val Arg Phe Leu Met Leu Val Gly Gly Ser Th - #r Leu Cys Val Arg Glu     
#               255                                                       
- Phe Gly Asn Met Ala Ser Pro Ala Pro Pro Al - #a Cys Asp Leu Arg Val     
#           270                                                           
- Leu Ser Lys Leu Leu Arg Asp Ser His Val Le - #u His Ser Arg Leu Ser     
#       285                                                               
- Gln Cys Pro Glu Val His Pro Leu Pro Thr Pr - #o Val Leu Leu Pro Ala     
#   300                                                                   
- Val                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:220:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:220:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Gly Glu Trp Lys Thr Gln Met Glu Gl - #u Thr Lys Ala Gln Asp     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gl - #y Val Met Ala Ala Arg     
#               175                                                       
- Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Le - #u Leu Gly Gln Leu Ser     
#           190                                                           
- Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gl - #n Ser Leu Leu Gly Thr     
#       205                                                               
- Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala Hi - #s Lys Asp Pro Asn Ala     
#   220                                                                   
- Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gl - #y Lys Val Arg Phe Leu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Met Leu Val Gly Gly Ser Thr Leu Cys Val Ar - #g Glu Phe Gly Asn Met     
#               255                                                       
- Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Ar - #g Val Leu Ser Lys Leu     
#           270                                                           
- Leu Arg Asp Ser His Val Leu His Ser Arg Le - #u Ser Gln Cys Pro Glu     
#       285                                                               
- Val His Pro Leu Pro Thr Pro Val Leu Leu Pr - #o Ala Val Asp Phe Ser     
#   300                                                                   
- Leu                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:221:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:221:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Gly Pro Thr Cys Leu Ser Ser Leu Le - #u Gly Gln Leu Ser Gly     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Se - #r Leu Leu Gly Thr Gln     
#               175                                                       
- Leu Pro Pro Gln Gly Arg Thr Thr Ala His Ly - #s Asp Pro Asn Ala Ile     
#           190                                                           
- Phe Leu Ser Phe Gln His Leu Leu Arg Gly Ly - #s Val Arg Phe Leu Met     
#       205                                                               
- Leu Val Gly Gly Ser Thr Leu Cys Val Arg Gl - #u Phe Gly Asn Met Ala     
#   220                                                                   
- Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Va - #l Leu Ser Lys Leu Leu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Arg Asp Ser His Val Leu His Ser Arg Leu Se - #r Gln Cys Pro Glu Val     
#               255                                                       
- His Pro Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
#           270                                                           
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#       285                                                               
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#   300                                                                   
- Leu                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:222:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:222:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Gly Thr Gln Leu Pro Pro Gln Gly Ar - #g Thr Thr Ala His Lys     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln Hi - #s Leu Leu Arg Gly Lys     
#               175                                                       
- Val Arg Phe Leu Met Leu Val Gly Gly Ser Th - #r Leu Cys Val Arg Glu     
#           190                                                           
- Phe Gly Asn Met Ala Ser Pro Ala Pro Pro Al - #a Cys Asp Leu Arg Val     
#       205                                                               
- Leu Ser Lys Leu Leu Arg Asp Ser His Val Le - #u His Ser Arg Leu Ser     
#   220                                                                   
- Gln Cys Pro Glu Val His Pro Leu Pro Thr Pr - #o Val Leu Leu Pro Ala     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gl - #n Met Glu Glu Thr Lys     
#               255                                                       
- Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Le - #u Leu Glu Gly Val Met     
#           270                                                           
- Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Le - #u Ser Ser Leu Leu Gly     
#       285                                                               
- Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gl - #y Ala Leu Gln Ser Leu     
#   300                                                                   
- Leu                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:223:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:223:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Gly Arg Thr Thr Ala His Lys Asp Pr - #o Asn Ala Ile Phe Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ser Phe Gln His Leu Leu Arg Gly Lys Val Ar - #g Phe Leu Met Leu Val     
#               175                                                       
- Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gl - #y Asn Met Ala Ser Pro     
#           190                                                           
- Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Se - #r Lys Leu Leu Arg Asp     
#       205                                                               
- Ser His Val Leu His Ser Arg Leu Ser Gln Cy - #s Pro Glu Val His Pro     
#   220                                                                   
- Leu Pro Thr Pro Val Leu Leu Pro Ala Val As - #p Phe Ser Leu Gly Glu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gl - #n Asp Ile Leu Gly Ala     
#               255                                                       
- Val Thr Leu Leu Leu Glu Gly Val Met Ala Al - #a Arg Gly Gln Leu Gly     
#           270                                                           
- Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Le - #u Ser Gly Gln Val Arg     
#       285                                                               
- Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gl - #y Thr Gln Leu Pro Pro     
#   300                                                                   
- Gln                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:224:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:224:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Gly Arg Thr Thr Ala His Lys Asp Pr - #o Asn Ala Ile Phe Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ser Phe Gln His Leu Leu Arg Gly Lys Val Ar - #g Phe Leu Met Leu Val     
#               175                                                       
- Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gl - #y Asn Met Ala Ser Pro     
#           190                                                           
- Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Se - #r Lys Leu Leu Arg Asp     
#       205                                                               
- Ser His Val Leu His Ser Arg Leu Ser Gln Cy - #s Pro Glu Val His Pro     
#   220                                                                   
- Leu Pro Thr Pro Val Leu Leu Pro Ala Val As - #p Phe Ser Leu Gly Glu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gl - #n Asp Ile Leu Gly Ala     
#               255                                                       
- Val Thr Leu Leu Leu Glu Gly Val Met Ala Al - #a Arg Gly Gln Leu Gly     
#           270                                                           
- Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Le - #u Ser Gly Gln Val Arg     
#       285                                                               
- Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gl - #y Thr Gln Leu Pro Pro     
#   300                                                                   
- Gln                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:225:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:225:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Asp Pro Asn Ala Ile Phe Leu Ser Ph - #e Gln His Leu Leu Arg     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gly Lys Val Arg Phe Leu Met Leu Val Gly Gl - #y Ser Thr Leu Cys Val     
#               175                                                       
- Arg Glu Phe Gly Asn Met Ala Ser Pro Ala Pr - #o Pro Ala Cys Asp Leu     
#           190                                                           
- Arg Val Leu Ser Lys Leu Leu Arg Asp Ser Hi - #s Val Leu His Ser Arg     
#       205                                                               
- Leu Ser Gln Cys Pro Glu Val His Pro Leu Pr - #o Thr Pro Val Leu Leu     
#   220                                                                   
- Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Ly - #s Thr Gln Met Glu Glu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Th - #r Leu Leu Leu Glu Gly     
#               255                                                       
- Val Met Ala Ala Arg Gly Gln Leu Gly Pro Th - #r Cys Leu Ser Ser Leu     
#           270                                                           
- Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Le - #u Leu Gly Ala Leu Gln     
#       285                                                               
- Ser Leu Leu Gly Thr Gln Leu Pro Pro Gln Gl - #y Arg Thr Thr Ala His     
#   300                                                                   
- Lys                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:226:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 305 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:226:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Ala Ile Phe Leu Ser Phe Gln His Le - #u Leu Arg Gly Lys Val     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Arg Phe Leu Met Leu Val Gly Gly Ser Thr Le - #u Cys Val Arg Glu Phe     
#               175                                                       
- Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cy - #s Asp Leu Arg Val Leu     
#           190                                                           
- Ser Lys Leu Leu Arg Asp Ser His Val Leu Hi - #s Ser Arg Leu Ser Gln     
#       205                                                               
- Cys Pro Glu Val His Pro Leu Pro Thr Pro Va - #l Leu Leu Pro Ala Val     
#   220                                                                   
- Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Me - #t Glu Glu Thr Lys Ala     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Le - #u Glu Gly Val Met Ala     
#               255                                                       
- Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Se - #r Ser Leu Leu Gly Gln     
#           270                                                           
- Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Al - #a Leu Gln Ser Leu Leu     
#       285                                                               
- Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Th - #r Ala His Lys Asp Pro     
#   300                                                                   
- Asn                                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:227:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 309 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:227:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#               175                                                       
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#           190                                                           
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#       205                                                               
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Leu     
#   220                                                                   
- Pro Pro Gln Gly Arg Thr Thr Ala His Lys As - #p Pro Asn Ala Ile Phe     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Ser Phe Gln His Leu Leu Arg Gly Lys Va - #l Arg Phe Leu Met Leu     
#               255                                                       
- Val Gly Gly Ser Thr Leu Cys Val Arg Glu Ph - #e Gly Gly Asn Gly Gly     
#           270                                                           
- Asn Met Ala Ser Pro Ala Pro Pro Ala Cys As - #p Leu Arg Val Leu Ser     
#       285                                                               
- Lys Leu Leu Arg Asp Ser His Val Leu His Se - #r Arg Leu Ser Gln Cys     
#   300                                                                   
- Pro Glu Val His Pro                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:228:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 309 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:228:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#               175                                                       
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#           190                                                           
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#       205                                                               
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Leu     
#   220                                                                   
- Pro Pro Gln Gly Arg Thr Thr Ala His Lys As - #p Pro Asn Ala Ile Phe     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Ser Phe Gln His Leu Leu Arg Gly Lys Va - #l Arg Phe Leu Met Leu     
#               255                                                       
- Val Gly Gly Ser Thr Leu Cys Val Arg Glu Ph - #e Gly Gly Asn Gly Gly     
#           270                                                           
- Asn Met Ala Ser Pro Ala Pro Pro Ala Cys As - #p Leu Arg Val Leu Ser     
#       285                                                               
- Lys Leu Leu Arg Asp Ser His Val Leu His Se - #r Arg Leu Ser Gln Cys     
#   300                                                                   
- Pro Glu Val His Pro                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:229:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 309 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:229:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Val Leu Leu Pro Ala Val Asp Phe Se - #r Leu Gly Glu Trp Lys     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Il - #e Leu Gly Ala Val Thr     
#               175                                                       
- Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gl - #y Gln Leu Gly Pro Thr     
#           190                                                           
- Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gl - #y Gln Val Arg Leu Leu     
#       205                                                               
- Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gl - #n Leu Pro Pro Gln Gly     
#   220                                                                   
- Arg Thr Thr Ala His Lys Asp Pro Asn Ala Il - #e Phe Leu Ser Phe Gln     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- His Leu Leu Arg Gly Lys Val Arg Phe Leu Me - #t Leu Val Gly Gly Ser     
#               255                                                       
- Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Gl - #y Gly Asn Met Ala Ser     
#           270                                                           
- Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Le - #u Ser Lys Leu Leu Arg     
#       285                                                               
- Asp Ser His Val Leu His Ser Arg Leu Ser Gl - #n Cys Pro Glu Val His     
#   300                                                                   
- Pro Leu Pro Thr Pro                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:230:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 309 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:230:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Ala Val Asp Phe Ser Leu Gly Glu Tr - #p Lys Thr Gln Met Glu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Va - #l Thr Leu Leu Leu Glu     
#               175                                                       
- Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pr - #o Thr Cys Leu Ser Ser     
#           190                                                           
- Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Le - #u Leu Leu Gly Ala Leu     
#       205                                                               
- Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gl - #n Gly Arg Thr Thr Ala     
#   220                                                                   
- His Lys Asp Pro Asn Ala Ile Phe Leu Ser Ph - #e Gln His Leu Leu Arg     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Gly Lys Val Arg Phe Leu Met Leu Val Gly Gl - #y Ser Thr Leu Cys Val     
#               255                                                       
- Arg Glu Phe Gly Gly Asn Gly Gly Asn Met Al - #a Ser Pro Ala Pro Pro     
#           270                                                           
- Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Le - #u Arg Asp Ser His Val     
#       285                                                               
- Leu His Ser Arg Leu Ser Gln Cys Pro Glu Va - #l His Pro Leu Pro Thr     
#   300                                                                   
- Pro Val Leu Leu Pro                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:231:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 309 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:231:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Asp Phe Ser Leu Gly Glu Trp Lys Th - #r Gln Met Glu Glu Thr     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Le - #u Leu Leu Glu Gly Val     
#               175                                                       
- Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cy - #s Leu Ser Ser Leu Leu     
#           190                                                           
- Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Le - #u Gly Ala Leu Gln Ser     
#       205                                                               
- Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Ar - #g Thr Thr Ala His Lys     
#   220                                                                   
- Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln Hi - #s Leu Leu Arg Gly Lys     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Val Arg Phe Leu Met Leu Val Gly Gly Ser Th - #r Leu Cys Val Arg Glu     
#               255                                                       
- Phe Gly Gly Asn Gly Gly Asn Met Ala Ser Pr - #o Ala Pro Pro Ala Cys     
#           270                                                           
- Asp Leu Arg Val Leu Ser Lys Leu Leu Arg As - #p Ser His Val Leu His     
#       285                                                               
- Ser Arg Leu Ser Gln Cys Pro Glu Val His Pr - #o Leu Pro Thr Pro Val     
#   300                                                                   
- Leu Leu Pro Ala Val                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:232:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 309 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:232:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Gly Glu Trp Lys Thr Gln Met Glu Gl - #u Thr Lys Ala Gln Asp     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gl - #y Val Met Ala Ala Arg     
#               175                                                       
- Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Le - #u Leu Gly Gln Leu Ser     
#           190                                                           
- Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gl - #n Ser Leu Leu Gly Thr     
#       205                                                               
- Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala Hi - #s Lys Asp Pro Asn Ala     
#   220                                                                   
- Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gl - #y Lys Val Arg Phe Leu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Met Leu Val Gly Gly Ser Thr Leu Cys Val Ar - #g Glu Phe Gly Gly Asn     
#               255                                                       
- Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Al - #a Cys Asp Leu Arg Val     
#           270                                                           
- Leu Ser Lys Leu Leu Arg Asp Ser His Val Le - #u His Ser Arg Leu Ser     
#       285                                                               
- Gln Cys Pro Glu Val His Pro Leu Pro Thr Pr - #o Val Leu Leu Pro Ala     
#   300                                                                   
- Val Asp Phe Ser Leu                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:233:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 309 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:233:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Gly Pro Thr Cys Leu Ser Ser Leu Le - #u Gly Gln Leu Ser Gly     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Se - #r Leu Leu Gly Thr Gln     
#               175                                                       
- Leu Pro Pro Gln Gly Arg Thr Thr Ala His Ly - #s Asp Pro Asn Ala Ile     
#           190                                                           
- Phe Leu Ser Phe Gln His Leu Leu Arg Gly Ly - #s Val Arg Phe Leu Met     
#       205                                                               
- Leu Val Gly Gly Ser Thr Leu Cys Val Arg Gl - #u Phe Gly Gly Asn Gly     
#   220                                                                   
- Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cy - #s Asp Leu Arg Val Leu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ser Lys Leu Leu Arg Asp Ser His Val Leu Hi - #s Ser Arg Leu Ser Gln     
#               255                                                       
- Cys Pro Glu Val His Pro Leu Pro Thr Pro Va - #l Leu Leu Pro Ala Val     
#           270                                                           
- Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Me - #t Glu Glu Thr Lys Ala     
#       285                                                               
- Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Le - #u Glu Gly Val Met Ala     
#   300                                                                   
- Ala Arg Gly Gln Leu                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:234:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 309 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:234:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Gly Thr Gln Leu Pro Pro Gln Gly Ar - #g Thr Thr Ala His Lys     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln Hi - #s Leu Leu Arg Gly Lys     
#               175                                                       
- Val Arg Phe Leu Met Leu Val Gly Gly Ser Th - #r Leu Cys Val Arg Glu     
#           190                                                           
- Phe Gly Gly Asn Gly Gly Asn Met Ala Ser Pr - #o Ala Pro Pro Ala Cys     
#       205                                                               
- Asp Leu Arg Val Leu Ser Lys Leu Leu Arg As - #p Ser His Val Leu His     
#   220                                                                   
- Ser Arg Leu Ser Gln Cys Pro Glu Val His Pr - #o Leu Pro Thr Pro Val     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Gl - #u Trp Lys Thr Gln Met     
#               255                                                       
- Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly Al - #a Val Thr Leu Leu Leu     
#           270                                                           
- Glu Gly Val Met Ala Ala Arg Gly Gln Leu Gl - #y Pro Thr Cys Leu Ser     
#       285                                                               
- Ser Leu Leu Gly Gln Leu Ser Gly Gln Val Ar - #g Leu Leu Leu Gly Ala     
#   300                                                                   
- Leu Gln Ser Leu Leu                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:235:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 309 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:235:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Gly Arg Thr Thr Ala His Lys Asp Pr - #o Asn Ala Ile Phe Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ser Phe Gln His Leu Leu Arg Gly Lys Val Ar - #g Phe Leu Met Leu Val     
#               175                                                       
- Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gl - #y Gly Asn Gly Gly Asn     
#           190                                                           
- Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Le - #u Arg Val Leu Ser Lys     
#       205                                                               
- Leu Leu Arg Asp Ser His Val Leu His Ser Ar - #g Leu Ser Gln Cys Pro     
#   220                                                                   
- Glu Val His Pro Leu Pro Thr Pro Val Leu Le - #u Pro Ala Val Asp Phe     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Gl - #u Thr Lys Ala Gln Asp     
#               255                                                       
- Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gl - #y Val Met Ala Ala Arg     
#           270                                                           
- Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Le - #u Leu Gly Gln Leu Ser     
#       285                                                               
- Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gl - #n Ser Leu Leu Gly Thr     
#   300                                                                   
- Gln Leu Pro Pro Gln                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:236:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 309 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:236:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Ala His Lys Asp Pro Asn Ala Ile Ph - #e Leu Ser Phe Gln His     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Leu Leu Arg Gly Lys Val Arg Phe Leu Met Le - #u Val Gly Gly Ser Thr     
#               175                                                       
- Leu Cys Val Arg Glu Phe Gly Gly Asn Gly Gl - #y Asn Met Ala Ser Pro     
#           190                                                           
- Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Se - #r Lys Leu Leu Arg Asp     
#       205                                                               
- Ser His Val Leu His Ser Arg Leu Ser Gln Cy - #s Pro Glu Val His Pro     
#   220                                                                   
- Leu Pro Thr Pro Val Leu Leu Pro Ala Val As - #p Phe Ser Leu Gly Glu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gl - #n Asp Ile Leu Gly Ala     
#               255                                                       
- Val Thr Leu Leu Leu Glu Gly Val Met Ala Al - #a Arg Gly Gln Leu Gly     
#           270                                                           
- Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Le - #u Ser Gly Gln Val Arg     
#       285                                                               
- Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gl - #y Thr Gln Leu Pro Pro     
#   300                                                                   
- Gln Gly Arg Thr Thr                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:237:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 309 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:237:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Asp Pro Asn Ala Ile Phe Leu Ser Ph - #e Gln His Leu Leu Arg     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gly Lys Val Arg Phe Leu Met Leu Val Gly Gl - #y Ser Thr Leu Cys Val     
#               175                                                       
- Arg Glu Phe Gly Gly Asn Gly Gly Asn Met Al - #a Ser Pro Ala Pro Pro     
#           190                                                           
- Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Le - #u Arg Asp Ser His Val     
#       205                                                               
- Leu His Ser Arg Leu Ser Gln Cys Pro Glu Va - #l His Pro Leu Pro Thr     
#   220                                                                   
- Pro Val Leu Leu Pro Ala Val Asp Phe Ser Le - #u Gly Glu Trp Lys Thr     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Le - #u Gly Ala Val Thr Leu     
#               255                                                       
- Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gl - #n Leu Gly Pro Thr Cys     
#           270                                                           
- Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gl - #n Val Arg Leu Leu Leu     
#       285                                                               
- Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Le - #u Pro Pro Gln Gly Arg     
#   300                                                                   
- Thr Thr Ala His Lys                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:238:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 309 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:238:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Ala Ile Phe Leu Ser Phe Gln His Le - #u Leu Arg Gly Lys Val     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Arg Phe Leu Met Leu Val Gly Gly Ser Thr Le - #u Cys Val Arg Glu Phe     
#               175                                                       
- Gly Gly Asn Gly Gly Asn Met Ala Ser Pro Al - #a Pro Pro Ala Cys Asp     
#           190                                                           
- Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Se - #r His Val Leu His Ser     
#       205                                                               
- Arg Leu Ser Gln Cys Pro Glu Val His Pro Le - #u Pro Thr Pro Val Leu     
#   220                                                                   
- Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Tr - #p Lys Thr Gln Met Glu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Va - #l Thr Leu Leu Leu Glu     
#               255                                                       
- Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pr - #o Thr Cys Leu Ser Ser     
#           270                                                           
- Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Le - #u Leu Leu Gly Ala Leu     
#       285                                                               
- Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gl - #n Gly Arg Thr Thr Ala     
#   300                                                                   
- His Lys Asp Pro Asn                                                     
305                                                                       
- (2) INFORMATION FOR SEQ ID NO:239:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 302 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:239:                           
- Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Il - #e His His Leu Lys Arg     
#                15                                                       
- Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Le - #u Asn Asp Glu Asp Val     
#            30                                                           
- Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pr - #o Asn Leu Glu Ser Phe     
#        45                                                               
- Val Arg Ala Val Lys Asn Leu Glu Asn Ala Se - #r Gly Ile Glu Ala Ile     
#    60                                                                   
- Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Al - #a Thr Ala Ala Pro Ser     
#80                                                                       
- Arg His Pro Ile Ile Ile Lys Ala Gly Asp Tr - #p Gln Glu Phe Arg Glu     
#                95                                                       
- Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gl - #n Ala Gln Glu Gln Gln     
#           110                                                           
- Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl - #u Pro Ser Gly Pro Ile     
#       125                                                               
- Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Gl - #u Ser His Lys Ser Pro     
#   140                                                                   
- Asn Met Asp Pro Asn Ala Ile Phe Leu Ser Ph - #e Gln His Leu Leu Arg     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gly Lys Val Arg Phe Leu Met Leu Val Gly Gl - #y Ser Thr Leu Cys Val     
#               175                                                       
- Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Al - #a Pro Pro Ala Cys Asp     
#           190                                                           
- Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Se - #r His Val Leu His Ser     
#       205                                                               
- Arg Leu Ser Gln Cys Pro Glu Val His Pro Le - #u Pro Thr Pro Val Leu     
#   220                                                                   
- Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Tr - #p Lys Thr Gln Met Glu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Va - #l Thr Leu Leu Leu Glu     
#               255                                                       
- Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pr - #o Thr Cys Leu Ser Ser     
#           270                                                           
- Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Le - #u Leu Leu Gly Ala Leu     
#       285                                                               
- Gln Ser Leu Leu Gly Thr Gln Gly Arg Thr Th - #r Ala His Lys             
#   300                                                                   
- (2) INFORMATION FOR SEQ ID NO:240:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 83 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:240:                           
- AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA GAACGCGCAG GC - #TCAACAGT   
  60                                                                      
#                83AGGC TCC                                               
- (2) INFORMATION FOR SEQ ID NO:241:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 83 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:241:                           
- CCGGGGAGCC TCCACCGCCC TCTACGTACT GTTGAGCCTG CGCGTTCTCC AA - #GGTTTTCA   
  60                                                                      
#                83ACGA CGG                                               
- (2) INFORMATION FOR SEQ ID NO:242:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 8 amino                                             
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:242:                           
- Gly Gly Gly Ser Gly Gly Gly Ser                                         
1               5                                                         
- (2) INFORMATION FOR SEQ ID NO:243:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 12 amino                                            
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:243:                           
- Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gl - #y Ser                     
#                10                                                       
- (2) INFORMATION FOR SEQ ID NO:244:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 7 amino                                             
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:244:                           
- Ser Gly Gly Ser Gly Gly Ser                                             
1               5                                                         
- (2) INFORMATION FOR SEQ ID NO:245:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 6 amino                                             
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:245:                           
- Glu Phe Gly Asn Met Ala                                                 
1               5                                                         
- (2) INFORMATION FOR SEQ ID NO:246:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 7 amino                                             
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:246:                           
- Glu Phe Gly Gly Asn Met Ala                                             
1               5                                                         
- (2) INFORMATION FOR SEQ ID NO:247:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 10 amino                                            
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:247:                           
- Glu Phe Gly Gly Asn Gly Gly Asn Met Ala                                 
#                10                                                       
- (2) INFORMATION FOR SEQ ID NO:248:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 7 amino                                             
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:248:                           
- Gly Gly Ser Asp Met Ala Gly                                             
1               5                                                         
- (2) INFORMATION FOR SEQ ID NO:249:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 459 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "SYNTHETIC"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:249:                           
- TCTCCCGCTC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TG - #ACTCCCAT   
  60                                                                      
- GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC AC - #CTGTCCTG   
 120                                                                      
- CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GA - #CCAAGGCA   
 180                                                                      
- CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC AC - #GGGGACAA   
 240                                                                      
- CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CC - #GTCTCCTC   
 300                                                                      
- CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GA - #CCACAGCT   
 360                                                                      
- CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AA - #AGGTGCGT   
 420                                                                      
#   459            GAGG GTCCACCCTC TGCGTCAGG                              
- (2) INFORMATION FOR SEQ ID NO:250:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 447 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "SYNTHETIC"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:250:                           
- TCTCCCGCTC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TG - #ACTCCCAT   
  60                                                                      
- GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC AC - #CTGTCCTG   
 120                                                                      
- CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GA - #CCAAGGCA   
 180                                                                      
- CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC AC - #GGGGACAA   
 240                                                                      
- CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CC - #GTCTCCTC   
 300                                                                      
- CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGGGCAGGA CCACAGCTCA CA - #AGGATCCC   
 360                                                                      
- AATGCCATCT TCCTGAGCTT CCAACACCTG CTCCGAGGAA AGGTGCGTTT CC - #TGATGCTT   
 420                                                                      
#            447   TCTG CGTCAGG                                           
- (2) INFORMATION FOR SEQ ID NO:251:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 459 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "SYNTHETIC"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:251:                           
- TCCCCAGCGC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TG - #ACTCCCAT   
  60                                                                      
- GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC AC - #CTGTCCTG   
 120                                                                      
- CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GA - #CCAAGGCA   
 180                                                                      
- CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC AC - #GGGGACAA   
 240                                                                      
- CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CC - #GTCTCCTC   
 300                                                                      
- CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GA - #CCACAGCT   
 360                                                                      
- CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AA - #AGGTGCGT   
 420                                                                      
#   459            GAGG GTCCACCCTC TGCGTCAGG                              
- (2) INFORMATION FOR SEQ ID NO:252:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 153 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:252:                           
- Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Va - #l Leu Ser Lys Leu Leu     
#                15                                                       
- Arg Asp Ser His Val Leu His Ser Arg Leu Se - #r Gln Cys Pro Glu Val     
#            30                                                           
- His Pro Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
#        45                                                               
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#    60                                                                   
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#80                                                                       
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#                95                                                       
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Leu     
#           110                                                           
- Pro Pro Gln Gly Arg Thr Thr Ala His Lys As - #p Pro Asn Ala Ile Phe     
#       125                                                               
- Leu Ser Phe Gln His Leu Leu Arg Gly Lys Va - #l Arg Phe Leu Met Leu     
#   140                                                                   
- Val Gly Gly Ser Thr Leu Cys Val Arg                                     
145                 1 - #50                                               
- (2) INFORMATION FOR SEQ ID NO:253:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 149 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:253:                           
- Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Va - #l Leu Ser Lys Leu Leu     
#                15                                                       
- Arg Asp Ser His Val Leu His Ser Arg Leu Se - #r Gln Cys Pro Glu Val     
#            30                                                           
- His Pro Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
#        45                                                               
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#    60                                                                   
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#80                                                                       
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#                95                                                       
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Gly     
#           110                                                           
- Arg Thr Thr Ala His Lys Asp Pro Asn Ala Il - #e Phe Leu Ser Phe Gln     
#       125                                                               
- His Leu Leu Arg Gly Lys Val Arg Phe Leu Me - #t Leu Val Gly Gly Ser     
#   140                                                                   
- Thr Leu Cys Val Arg                                                     
145                                                                       
- (2) INFORMATION FOR SEQ ID NO:254:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 153 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:254:                           
- Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Va - #l Leu Ser Lys Leu Leu     
#                15                                                       
- Arg Asp Ser His Val Leu His Ser Arg Leu Se - #r Gln Cys Pro Glu Val     
#            30                                                           
- His Pro Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
#        45                                                               
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#    60                                                                   
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#80                                                                       
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#                95                                                       
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Leu     
#           110                                                           
- Pro Pro Gln Gly Arg Thr Thr Ala His Lys As - #p Pro Asn Ala Ile Phe     
#       125                                                               
- Leu Ser Phe Gln His Leu Leu Arg Gly Lys Va - #l Arg Phe Leu Met Leu     
#   140                                                                   
- Val Gly Gly Ser Thr Leu Cys Val Arg                                     
145                 1 - #50                                               
- (2) INFORMATION FOR SEQ ID NO:255:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 64 base                                             
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "SYNTHETIC"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:255:                           
- GGATCCACCA TGAGCCGCCT GCCCGTCCTG CTCCTGCTCC AACTCCTGGT CC - #GCCCCGCC   
  60                                                                      
#             64                                                          
- (2) INFORMATION FOR SEQ ID NO:256:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 153 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: protein                                         
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 112                                               
#/note= "position 112 is deleted or                                       
               Leu, Ala, - #VAl, Ile, Pro, Phe, Trp or Met"               
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 113                                               
#/note= "positoin 113 is deleted or                                       
               Pro, Phe, - # Ala, Val, Leu, Ile, Trp or Met"              
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 114                                               
#/note= "position 114 is deleted or                                       
               Pro, Phe, - # Ala, Val, Leu, Ile, Trp or Met"              
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 115                                               
#/note= "positon 115 is deleted or                                        
               Gln, Gly, - # Ser, Thr, Tyr, or Asn"                       
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:256:                           
- Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Va - #l Leu Ser Lys Leu Leu     
#                15                                                       
- Arg Asp Ser His Val Leu His Ser Arg Leu Se - #r Gln Cys Pro Glu Val     
#            30                                                           
- His Pro Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
#        45                                                               
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#    60                                                                   
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#80                                                                       
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#                95                                                       
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Xaa     
#           110                                                           
- Xaa Xaa Xaa Gly Arg Thr Thr Ala His Lys As - #p Pro Asn Ala Ile Phe     
#       125                                                               
- Leu Ser Phe Gln His Leu Leu Arg Gly Lys Va - #l Arg Phe Leu Met Leu     
#   140                                                                   
- Val Gly Gly Ser Thr Leu Cys Val Arg                                     
145                 1 - #50                                               
- (2) INFORMATION FOR SEQ ID NO:257:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 464 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "SYNTHETIC"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:257:                           
- CCATGGCTAA CTGCTCTATA ATGATCGATG AAATTATACA TCACTTAAAG AG - #ACCACCTG   
  60                                                                      
- CACCTTTGCT GGACCCGAAC AACCTCAATG ACGAAGACGT CTCTATCCTG AT - #GGATCGAA   
 120                                                                      
- ACCTTCGACT TCCAAACCTG GAGAGCTTCG TAAGGGCTGT CAAGAACTTA GA - #AAATGCAT   
 180                                                                      
- CAGGTATTGA GGCAATTCTT CGTAATCTCC AACCATGTCT GCCCTCTGCC AC - #GGCCGCAC   
 240                                                                      
- CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA AGAATTCCGG GA - #AAAACTGA   
 300                                                                      
- CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GTACGTAGAG GG - #CGGTGGAG   
 360                                                                      
- GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CCCGTCTCCT CC - #GTCTAAAG   
 420                                                                      
#464               AAAC ATGTAAGGTA CCGCATGCAA GCTT                        
- (2) INFORMATION FOR SEQ ID NO:258:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 100 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "SYNTHETIC"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:258:                           
- AAAACAAGAA GAAAGGCGAT AAAAAGGTTG TGGTAAGAGA AATGGATAAA AA - #GGGGTCGG   
  60                                                                      
#   100            TTAA AAAAGAGGAA GTAGGTCAAG                             
- (2) INFORMATION FOR SEQ ID NO:259:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 11808 base                                          
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:259:                           
- ACGTACTCCA TGGCTAACTG CTCTATAATG ATCGATGAAA TTATACATCA CT - #TAAAGAGA   
  60                                                                      
- CCACCTGCAC CTTTGCTGGA CCCGAACAAC CTCAATGACG AAGACGTCTC TA - #TCCTGATG   
 120                                                                      
- GATCGAAACC TTCGACTTCC AAACCTGGAG AGCTTCGTAA GGGCTGTCAA GA - #ACTTAGAA   
 180                                                                      
- AATGCATCAG GTATTGAGGC AATTCTTCGT AATCTCCAAC CATGTCTGCC CT - #CTGCCACG   
 240                                                                      
- GCCGCACCCT CTCGACATCC AATCATCATC AAGGCAGGTG ACTGGCAAGA AT - #TCCGGGAA   
 300                                                                      
- AAACTGACGT TCTATCTGGT TACCCTTGAG CAAGCGCAGG AACAACAGTA CG - #TAGAGGGC   
 360                                                                      
- GGTGGAGGCT CCCCGGGTGA ACCGTCTGGT CCAATCTCTA CTATCAACCC GT - #CTCCTCCG   
 420                                                                      
- TCTAAAGAAT CTCATAAATC TCCAAACATG GCTTTAGGCC CTGCCAGCTC CC - #TGCCCCAG   
 480                                                                      
- AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG AGGAAGATCC AGGGCGATGG CG - #CAGCGCTC   
 540                                                                      
- CAGGAGAAGC TGTGTGCCAC CTACAAGCTG TGCCACCCCG AGGAGCTGGT GC - #TGCTCGGA   
 600                                                                      
- CACTCTCTGG GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC CC - #TGCAGCTG   
 660                                                                      
- GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT ACCAGGGGCT CC - #TGCAGGCC   
 720                                                                      
- CTGGAAGGGA TATCCCCCGA GTTGGGTCCC ACCTTGGACA CACTGCAGCT GG - #ACGTCGCC   
 780                                                                      
- GACTTTGCCA CCACCATCTG GCAGCAGATG GAAGAACTGG GAATGGCCCC TG - #CCCTGCAG   
 840                                                                      
- CCCACCCAGG GTGCCATGCC GGCCTTCGCC TCTGCTTTCC AGCGCCGGGC AG - #GAGGGGTC   
 900                                                                      
- CTGGTTGCTA GCCATCTGCA GAGCTTCCTG GAGGTGTCGT ACCGCGTTCT AC - #GCCACCTT   
 960                                                                      
- GCGCAGCCCG ACATGGCTAC ACCAACGTAC TCCATGGCTA ACTGCTCTAT AA - #TGATCGAT   
1020                                                                      
- GAAATTATAC ATCACTTAAA GAGACCACCT GCACCTTTGC TGGACCCGAA CA - #ACCTCAAT   
1080                                                                      
- GACGAAGACG TCTCTATCCT GATGGATCGA AACCTTCGAC TTCCAAACCT GG - #AGAGCTTC   
1140                                                                      
- GTAAGGGCTG TCAAGAACTT AGAAAATGCA TCAGGTATTG AGGCAATTCT TC - #GTAATCTC   
1200                                                                      
- CAACCATGTC TGCCCTCTGC CACGGCCGCA CCCTCTCGAC ATCCAATCAT CA - #TCAAGGCA   
1260                                                                      
- GGTGACTGGC AAGAATTCCG GGAAAAACTG ACGTTCTATC TGGTTACCCT TG - #AGCAAGCG   
1320                                                                      
- CAGGAACAAC AGTACGTAGA GGGCGGTGGA GGCTCCCCGG GTGAACCGTC TG - #GTCCAATC   
1380                                                                      
- TCTACTATCA ACCCGTCTCC TCCGTCTAAA GAATCTCATA AATCTCCAAA CA - #TGGCTCAG   
1440                                                                      
- AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG AGGAAGATCC AGGGCGATGG CG - #CAGCGCTC   
1500                                                                      
- CAGGAGAAGC TGTGTGCCAC CTACAAGCTG TGCCACCCCG AGGAGCTGGT GC - #TGCTCGGA   
1560                                                                      
- CACTCTCTGG GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC CC - #TGCAGCTG   
1620                                                                      
- GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT ACCAGGGGCT CC - #TGCAGGCC   
1680                                                                      
- CTGGAAGGGA TATCCCCCGA GTTGGGTCCC ACCTTGGACA CACTGCAGCT GG - #ACGTCGCC   
1740                                                                      
- GACTTTGCCA CCACCATCTG GCAGCAGATG GAAGAACTGG GAATGGCCCC TG - #CCCTGCAG   
1800                                                                      
- CCCACCCAGG GTGCCATGCC GGCCTTCGCC TCTGCTTTCC AGCGCCGGGC AG - #GAGGGGTC   
1860                                                                      
- CTGGTTGCTA GCCATCTGCA GAGCTTCCTG GAGGTGTCGT ACCGCGTTCT AC - #GCCACCTT   
1920                                                                      
- GCGCAGCCCG ACATGGCTAC ACCATTAGGC CCTGCCAGCT CCCTGCCCAC GT - #ACTCCATG   
1980                                                                      
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
2040                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA TC - #GAAACCTT   
2100                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
2160                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
2220                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
2280                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
2340                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
2400                                                                      
- CATAAATCTC CAAACATGGC TTTCCTGCTC AAGTCTTTAG AGCAAGTGAG GA - #AGATCCAG   
2460                                                                      
- GGCGATGGCG CAGCGCTCCA GGAGAAGCTG TGTGCCACCT ACAAGCTGTG CC - #ACCCCGAG   
2520                                                                      
- GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG CTCCCCTGAG CT - #CCTGCCCC   
2580                                                                      
- AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TT - #TCCTCTAC   
2640                                                                      
- CAGGGGCTCC TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CT - #TGGACACA   
2700                                                                      
- CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AG - #AACTGGGA   
2760                                                                      
- ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG CCTTCGCCTC TG - #CTTTCCAG   
2820                                                                      
- CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC CATCTGCAGA GCTTCCTGGA GG - #TGTCGTAC   
2880                                                                      
- CGCGTTCTAC GCCACCTTGC GCAGCCCGAC ATGGCTACAC CATTAGGCCC TG - #CCAGCTCC   
2940                                                                      
- CTGCCCCAGA GCACGTACTC CATGGCTAAC TGCTCTATAA TGATCGATGA AA - #TTATACAT   
3000                                                                      
- CACTTAAAGA GACCACCTGC ACCTTTGCTG GACCCGAACA ACCTCAATGA CG - #AAGACGTC   
3060                                                                      
- TCTATCCTGA TGGATCGAAA CCTTCGACTT CCAAACCTGG AGAGCTTCGT AA - #GGGCTGTC   
3120                                                                      
- AAGAACTTAG AAAATGCATC AGGTATTGAG GCAATTCTTC GTAATCTCCA AC - #CATGTCTG   
3180                                                                      
- CCCTCTGCCA CGGCCGCACC CTCTCGACAT CCAATCATCA TCAAGGCAGG TG - #ACTGGCAA   
3240                                                                      
- GAATTCCGGG AAAAACTGAC GTTCTATCTG GTTACCCTTG AGCAAGCGCA GG - #AACAACAG   
3300                                                                      
- TACGTAGAGG GCGGTGGAGG CTCCCCGGGT GAACCGTCTG GTCCAATCTC TA - #CTATCAAC   
3360                                                                      
- CCGTCTCCTC CGTCTAAAGA ATCTCATAAA TCTCCAAACA TGGCTGAGCA AG - #TGAGGAAG   
3420                                                                      
- ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG CCACCTACAA GC - #TGTGCCAC   
3480                                                                      
- CCCGAGGAGC TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CC - #TGAGCTCC   
3540                                                                      
- TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG CG - #GCCTTTTC   
3600                                                                      
- CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TC - #CCACCTTG   
3660                                                                      
- GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA GA - #TGGAAGAA   
3720                                                                      
- CTGGGAATGG CCCCTGCCCT GCAGCCCACC CAGGGTGCCA TGCCGGCCTT CG - #CCTCTGCT   
3780                                                                      
- TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT CC - #TGGAGGTG   
3840                                                                      
- TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCGACATGG CTACACCATT AG - #GCCCTGCC   
3900                                                                      
- AGCTCCCTGC CCCAGAGCTT CCTGCTCAAG TCTTTAACGT ACTCCATGGC TA - #ACTGCTCT   
3960                                                                      
- ATAATGATCG ATGAAATTAT ACATCACTTA AAGAGACCAC CTGCACCTTT GC - #TGGACCCG   
4020                                                                      
- AACAACCTCA ATGACGAAGA CGTCTCTATC CTGATGGATC GAAACCTTCG AC - #TTCCAAAC   
4080                                                                      
- CTGGAGAGCT TCGTAAGGGC TGTCAAGAAC TTAGAAAATG CATCAGGTAT TG - #AGGCAATT   
4140                                                                      
- CTTCGTAATC TCCAACCATG TCTGCCCTCT GCCACGGCCG CACCCTCTCG AC - #ATCCAATC   
4200                                                                      
- ATCATCAAGG CAGGTGACTG GCAAGAATTC CGGGAAAAAC TGACGTTCTA TC - #TGGTTACC   
4260                                                                      
- CTTGAGCAAG CGCAGGAACA ACAGTACGTA GAGGGCGGTG GAGGCTCCCC GG - #GTGAACCG   
4320                                                                      
- TCTGGTCCAA TCTCTACTAT CAACCCGTCT CCTCCGTCTA AAGAATCTCA TA - #AATCTCCA   
4380                                                                      
- AACATGGCTC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG CTCCCCTGAG CT - #CCTGCCCC   
4440                                                                      
- AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TT - #TCCTCTAC   
4500                                                                      
- CAGGGGCTCC TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CT - #TGGACACA   
4560                                                                      
- CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AG - #AACTGGGA   
4620                                                                      
- ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG CCTTCGCCTC TG - #CTTTCCAG   
4680                                                                      
- CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC CATCTGCAGA GCTTCCTGGA GG - #TGTCGTAC   
4740                                                                      
- CGCGTTCTAC GCCACCTTGC GCAGCCCGAC ATGGCTACAC CATTAGGCCC TG - #CCAGCTCC   
4800                                                                      
- CTGCCCCAGA GCTTCCTGCT CAAGTCTTTA GAGCAAGTGA GGAAGATCCA GG - #GCGATGGC   
4860                                                                      
- GCAGCGCTCC AGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GG - #AGCTGGTG   
4920                                                                      
- ACGTACTCCA TGGCTAACTG CTCTATAATG ATCGATGAAA TTATACATCA CT - #TAAAGAGA   
4980                                                                      
- CCACCTGCAC CTTTGCTGGA CCCGAACAAC CTCAATGACG AAGACGTCTC TA - #TCCTGATG   
5040                                                                      
- GATCGAAACC TTCGACTTCC AAACCTGGAG AGCTTCGTAA GGGCTGTCAA GA - #ACTTAGAA   
5100                                                                      
- AATGCATCAG GTATTGAGGC AATTCTTCGT AATCTCCAAC CATGTCTGCC CT - #CTGCCACG   
5160                                                                      
- GCCGCACCCT CTCGACATCC AATCATCATC AAGGCAGGTG ACTGGCAAGA AT - #TCCGGGAA   
5220                                                                      
- AAACTGACGT TCTATCTGGT TACCCTTGAG CAAGCGCAGG AACAACAGTA CG - #TAGAGGGC   
5280                                                                      
- GGTGGAGGCT CCCCGGGTGA ACCGTCTGGT CCAATCTCTA CTATCAACCC GT - #CTCCTCCG   
5340                                                                      
- TCTAAAGAAT CTCATAAATC TCCAAACATG GCTCCCCTGA GCTCCTGCCC CA - #GCCAGGCC   
5400                                                                      
- CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCC TTTTCCTCTA CC - #AGGGGCTC   
5460                                                                      
- CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG TTGGGTCCCA CCTTGGACAC AC - #TGCAGCTG   
5520                                                                      
- GACGTCGCCG ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AA - #TGGCCCCT   
5580                                                                      
- GCCCTGCAGC CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GC - #GCCGGGCA   
5640                                                                      
- GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CC - #GCGTTCTA   
5700                                                                      
- CGCCACCTTG CGCAGCCCGA CATGGCTACA CCATTAGGCC CTGCCAGCTC CC - #TGCCCCAG   
5760                                                                      
- AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG AGGAAGATCC AGGGCGATGG CG - #CAGCGCTC   
5820                                                                      
- CAGGAGAAGC TGTGTGCCAC CTACAAGCTG TGCCACCCCG AGGAGCTGGT GC - #TGCTCGGA   
5880                                                                      
- CACTCTCTGG GCATCCCCTG GGCTACGTAC TCCATGGCTA ACTGCTCTAT AA - #TGATCGAT   
5940                                                                      
- GAAATTATAC ATCACTTAAA GAGACCACCT GCACCTTTGC TGGACCCGAA CA - #ACCTCAAT   
6000                                                                      
- GACGAAGACG TCTCTATCCT GATGGATCGA AACCTTCGAC TTCCAAACCT GG - #AGAGCTTC   
6060                                                                      
- GTAAGGGCTG TCAAGAACTT AGAAAATGCA TCAGGTATTG AGGCAATTCT TC - #GTAATCTC   
6120                                                                      
- CAACCATGTC TGCCCTCTGC CACGGCCGCA CCCTCTCGAC ATCCAATCAT CA - #TCAAGGCA   
6180                                                                      
- GGTGACTGGC AAGAATTCCG GGAAAAACTG ACGTTCTATC TGGTTACCCT TG - #AGCAAGCG   
6240                                                                      
- CAGGAACAAC AGTACGTAGA GGGCGGTGGA GGCTCCCCGG GTGAACCGTC TG - #GTCCAATC   
6300                                                                      
- TCTACTATCA ACCCGTCTCC TCCGTCTAAA GAATCTCATA AATCTCCAAA CA - #TGGCTCAG   
6360                                                                      
- GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CT - #ACCAGGGG   
6420                                                                      
- CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC CCACCTTGGA CA - #CACTGCAG   
6480                                                                      
- CTGGACGTCG CCGACTTTGC CACCACCATC TGGCAGCAGA TGGAAGAACT GG - #GAATGGCC   
6540                                                                      
- CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT CC - #AGCGCCGG   
6600                                                                      
- GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GT - #ACCGCGTT   
6660                                                                      
- CTACGCCACC TTGCGCAGCC CGACATGGCT ACACCATTAG GCCCTGCCAG CT - #CCCTGCCC   
6720                                                                      
- CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGGAAGA TCCAGGGCGA TG - #GCGCAGCG   
6780                                                                      
- CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC CCGAGGAGCT GG - #TGCTGCTC   
6840                                                                      
- GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCAC GT - #ACTCCATG   
6900                                                                      
- GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC AC - #CTGCACCT   
6960                                                                      
- TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA TC - #GAAACCTT   
7020                                                                      
- CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TG - #CATCAGGT   
7080                                                                      
- ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CG - #CACCCTCT   
7140                                                                      
- CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA AC - #TGACGTTC   
7200                                                                      
- TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TG - #GAGGCTCC   
7260                                                                      
- CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TA - #AAGAATCT   
7320                                                                      
- CATAAATCTC CAAACATGGC TCTGCAGCTG GCAGGCTGCT TGAGCCAACT CC - #ATAGCGGC   
7380                                                                      
- CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GT - #TGGGTCCC   
7440                                                                      
- ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GC - #AGCAGATG   
7500                                                                      
- GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCACCCAGG GTGCCATGCC GG - #CCTTCGCC   
7560                                                                      
- TCTGCTTTCC AGCGCCGGGC AGGAGGGGTC CTGGTTGCTA GCCATCTGCA GA - #GCTTCCTG   
7620                                                                      
- GAGGTGTCGT ACCGCGTTCT ACGCCACCTT GCGCAGCCCG ACATGGCTAC AC - #CATTAGGC   
7680                                                                      
- CCTGCCAGCT CCCTGCCCCA GAGCTTCCTG CTCAAGTCTT TAGAGCAAGT GA - #GGAAGATC   
7740                                                                      
- CAGGGCGATG GCGCAGCGCT CCAGGAGAAG CTGTGTGCCA CCTACAAGCT GT - #GCCACCCC   
7800                                                                      
- GAGGAGCTGG TGCTGCTCGG ACACTCTCTG GGCATCCCCT GGGCTCCCCT GA - #GCTCCTGC   
7860                                                                      
- CCCAGCCAGG CCACGTACTC CATGGCTAAC TGCTCTATAA TGATCGATGA AA - #TTATACAT   
7920                                                                      
- CACTTAAAGA GACCACCTGC ACCTTTGCTG GACCCGAACA ACCTCAATGA CG - #AAGACGTC   
7980                                                                      
- TCTATCCTGA TGGATCGAAA CCTTCGACTT CCAAACCTGG AGAGCTTCGT AA - #GGGCTGTC   
8040                                                                      
- AAGAACTTAG AAAATGCATC AGGTATTGAG GCAATTCTTC GTAATCTCCA AC - #CATGTCTG   
8100                                                                      
- CCCTCTGCCA CGGCCGCACC CTCTCGACAT CCAATCATCA TCAAGGCAGG TG - #ACTGGCAA   
8160                                                                      
- GAATTCCGGG AAAAACTGAC GTTCTATCTG GTTACCCTTG AGCAAGCGCA GG - #AACAACAG   
8220                                                                      
- TACGTAGAGG GCGGTGGAGG CTCCCCGGGT GAACCGTCTG GTCCAATCTC TA - #CTATCAAC   
8280                                                                      
- CCGTCTCCTC CGTCTAAAGA ATCTCATAAA TCTCCAAACA TGGCTCTGGC AG - #GCTGCTTG   
8340                                                                      
- AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC TGCAGGCCCT GG - #AAGGGATA   
8400                                                                      
- TCCCCCGAGT TGGGTCCCAC CTTGGACACA CTGCAGCTGG ACGTCGCCGA CT - #TTGCCACC   
8460                                                                      
- ACCATCTGGC AGCAGATGGA AGAACTGGGA ATGGCCCCTG CCCTGCAGCC CA - #CCCAGGGT   
8520                                                                      
- GCCATGCCGG CCTTCGCCTC TGCTTTCCAG CGCCGGGCAG GAGGGGTCCT GG - #TTGCTAGC   
8580                                                                      
- CATCTGCAGA GCTTCCTGGA GGTGTCGTAC CGCGTTCTAC GCCACCTTGC GC - #AGCCCGAC   
8640                                                                      
- ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CA - #AGTCTTTA   
8700                                                                      
- GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GT - #GTGCCACC   
8760                                                                      
- TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CA - #TCCCCTGG   
8820                                                                      
- GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGACGT ACTCCATGGC TA - #ACTGCTCT   
8880                                                                      
- ATAATGATCG ATGAAATTAT ACATCACTTA AAGAGACCAC CTGCACCTTT GC - #TGGACCCG   
8940                                                                      
- AACAACCTCA ATGACGAAGA CGTCTCTATC CTGATGGATC GAAACCTTCG AC - #TTCCAAAC   
9000                                                                      
- CTGGAGAGCT TCGTAAGGGC TGTCAAGAAC TTAGAAAATG CATCAGGTAT TG - #AGGCAATT   
9060                                                                      
- CTTCGTAATC TCCAACCATG TCTGCCCTCT GCCACGGCCG CACCCTCTCG AC - #ATCCAATC   
9120                                                                      
- ATCATCAAGG CAGGTGACTG GCAAGAATTC CGGGAAAAAC TGACGTTCTA TC - #TGGTTACC   
9180                                                                      
- CTTGAGCAAG CGCAGGAACA ACAGTACGTA GAGGGCGGTG GAGGCTCCCC GG - #GTGAACCG   
9240                                                                      
- TCTGGTCCAA TCTCTACTAT CAACCCGTCT CCTCCGTCTA AAGAATCTCA TA - #AATCTCCA   
9300                                                                      
- AACATGGCTG AACTGGGAAT GGCCCCTGCC CTGCAGCCCA CCCAGGGTGC CA - #TGCCGGCC   
9360                                                                      
- TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA GGGGTCCTGG TTGCTAGCCA TC - #TGCAGAGC   
9420                                                                      
- TTCCTGGAGG TGTCGTACCG CGTTCTACGC CACCTTGCGC AGCCCGACAT GG - #CTACACCA   
9480                                                                      
- TTAGGCCCTG CCAGCTCCCT GCCCCAGAGC TTCCTGCTCA AGTCTTTAGA GC - #AAGTGAGG   
9540                                                                      
- AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CA - #AGCTGTGC   
9600                                                                      
- CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC TC - #CCCTGAGC   
9660                                                                      
- TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA GCCAACTCCA TA - #GCGGCCTT   
9720                                                                      
- TTCCTCTACC AGGGGCTCCT GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GG - #GTCCCACC   
9780                                                                      
- TTGGACACAC TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCA GC - #AGATGGAA   
9840                                                                      
- ACGTACTCCA TGGCTAACTG CTCTATAATG ATCGATGAAA TTATACATCA CT - #TAAAGAGA   
9900                                                                      
- CCACCTGCAC CTTTGCTGGA CCCGAACAAC CTCAATGACG AAGACGTCTC TA - #TCCTGATG   
9960                                                                      
- GATCGAAACC TTCGACTTCC AAACCTGGAG AGCTTCGTAA GGGCTGTCAA GA - #ACTTAGAA   
10020                                                                     
- AATGCATCAG GTATTGAGGC AATTCTTCGT AATCTCCAAC CATGTCTGCC CT - #CTGCCACG   
10080                                                                     
- GCCGCACCCT CTCGACATCC AATCATCATC AAGGCAGGTG ACTGGCAAGA AT - #TCCGGGAA   
10140                                                                     
- AAACTGACGT TCTATCTGGT TACCCTTGAG CAAGCGCAGG AACAACAGTA CG - #TAGAGGGC   
10200                                                                     
- GGTGGAGGCT CCCCGGGTGA ACCGTCTGGT CCAATCTCTA CTATCAACCC GT - #CTCCTCCG   
10260                                                                     
- TCTAAAGAAT CTCATAAATC TCCAAACATG GCTGGAATGG CCCCTGCCCT GC - #AGCCCACC   
10320                                                                     
- CAGGGTGCCA TGCCGGCCTT CGCCTCTGCT TTCCAGCGCC GGGCAGGAGG GG - #TCCTGGTT   
10380                                                                     
- GCTAGCCATC TGCAGAGCTT CCTGGAGGTG TCGTACCGCG TTCTACGCCA CC - #TTGCGCAG   
10440                                                                     
- CCCGACATGG CTACACCATT AGGCCCTGCC AGCTCCCTGC CCCAGAGCTT CC - #TGCTCAAG   
10500                                                                     
- TCTTTAGAGC AAGTGAGGAA GATCCAGGGC GATGGCGCAG CGCTCCAGGA GA - #AGCTGTGT   
10560                                                                     
- GCCACCTACA AGCTGTGCCA CCCCGAGGAG CTGGTGCTGC TCGGACACTC TC - #TGGGCATC   
10620                                                                     
- CCCTGGGCTC CCCTGAGCTC CTGCCCCAGC CAGGCCCTGC AGCTGGCAGG CT - #GCTTGAGC   
10680                                                                     
- CAACTCCATA GCGGCCTTTT CCTCTACCAG GGGCTCCTGC AGGCCCTGGA AG - #GGATATCC   
10740                                                                     
- CCCGAGTTGG GTCCCACCTT GGACACACTG CAGCTGGACG TCGCCGACTT TG - #CCACCACC   
10800                                                                     
- ATCTGGCAGC AGATGGAAGA ACTGACGTAC TCCATGGCTA ACTGCTCTAT AA - #TGATCGAT   
10860                                                                     
- GAAATTATAC ATCACTTAAA GAGACCACCT GCACCTTTGC TGGACCCGAA CA - #ACCTCAAT   
10920                                                                     
- GACGAAGACG TCTCTATCCT GATGGATCGA AACCTTCGAC TTCCAAACCT GG - #AGAGCTTC   
10980                                                                     
- GTAAGGGCTG TCAAGAACTT AGAAAATGCA TCAGGTATTG AGGCAATTCT TC - #GTAATCTC   
11040                                                                     
- CAACCATGTC TGCCCTCTGC CACGGCCGCA CCCTCTCGAC ATCCAATCAT CA - #TCAAGGCA   
11100                                                                     
- GGTGACTGGC AAGAATTCCG GGAAAAACTG ACGTTCTATC TGGTTACCCT TG - #AGCAAGCG   
11160                                                                     
- CAGGAACAAC AGTACGTAGA GGGCGGTGGA GGCTCCCCGG GTGAACCGTC TG - #GTCCAATC   
11220                                                                     
- TCTACTATCA ACCCGTCTCC TCCGTCTAAA GAATCTCATA AATCTCCAAA CA - #TGGCTAGC   
11280                                                                     
- TTCCTGGAGG TGTCGTACCG CGTTCTACGC CACCTTGCGC AGCCCGACAT GG - #CTACACCA   
11340                                                                     
- TTAGGCCCTG CCAGCTCCCT GCCCCAGAGC TTCCTGCTCA AGTCTTTAGA GC - #AAGTGAGG   
11400                                                                     
- AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CA - #AGCTGTGC   
11460                                                                     
- CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC TC - #CCCTGAGC   
11520                                                                     
- TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA GCCAACTCCA TA - #GCGGCCTT   
11580                                                                     
- TTCCTCTACC AGGGGCTCCT GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GG - #GTCCCACC   
11640                                                                     
- TTGGACACAC TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCA GC - #AGATGGAA   
11700                                                                     
- GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CT - #TCGCCTCT   
11760                                                                     
#             11808CAGG AGGGGTCCTG GTTGCTAGCC ATCTGCAG                    
- (2) INFORMATION FOR SEQ ID NO:260:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 975 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:260:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTCAGAGC TTCCTGCTCA AGTCTTTAGA GC - #AAGTGAGG   
 480                                                                      
- AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CA - #AGCTGTGC   
 540                                                                      
- CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC TC - #CCCTGAGC   
 600                                                                      
- TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA GCCAACTCCA TA - #GCGGCCTT   
 660                                                                      
- TTCCTCTACC AGGGGCTCCT GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GG - #GTCCCACC   
 720                                                                      
- TTGGACACAC TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCA GC - #AGATGGAA   
 780                                                                      
- GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CT - #TCGCCTCT   
 840                                                                      
- GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC ATCTGCAGAG CT - #TCCTGGAG   
 900                                                                      
- GTGTCGTACC GCGTTCTACG CCACCTTGCG CAGCCCGACA TGGCTACACC AT - #TAGGCCCT   
 960                                                                      
#   975                                                                   
- (2) INFORMATION FOR SEQ ID NO:261:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 975 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:261:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTCAGAGC TTCCTGCTCA AGTCTTTAGA GC - #AAGTGAGG   
 480                                                                      
- AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CA - #AGCTGTGC   
 540                                                                      
- CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC TC - #CCCTGAGC   
 600                                                                      
- TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA GCCAACTCCA TA - #GCGGCCTT   
 660                                                                      
- TTCCTCTACC AGGGGCTCCT GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GG - #GTCCCACC   
 720                                                                      
- TTGGACACAC TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCA GC - #AGATGGAA   
 780                                                                      
- GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CT - #TCGCCTCT   
 840                                                                      
- GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC ATCTGCAGAG CT - #TCCTGGAG   
 900                                                                      
- GTGTCGTACC GCGTTCTACG CCACCTTGCG CAGCCCGACA TGGCTACACC AT - #TAGGCCCT   
 960                                                                      
#   975                                                                   
- (2) INFORMATION FOR SEQ ID NO:262:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 975 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:262:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTGAGCAA GTGAGGAAGA TCCAGGGCGA TG - #GCGCAGCG   
 480                                                                      
- CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC CCGAGGAGCT GG - #TGCTGCTC   
 540                                                                      
- GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GG - #CCCTGCAG   
 600                                                                      
- CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GC - #TCCTGCAG   
 660                                                                      
- GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GC - #TGGACGTC   
 720                                                                      
- GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CC - #CTGCCCTG   
 780                                                                      
- CAGCCCACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GG - #CAGGAGGG   
 840                                                                      
- GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TC - #TACGCCAC   
 900                                                                      
- CTTGCGCAGC CCGACATGGC TACACCATTA GGCCCTGCCA GCTCCCTGCC CC - #AGAGCTTC   
 960                                                                      
#   975                                                                   
- (2) INFORMATION FOR SEQ ID NO:263:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 975 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:263:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTCTGCTC GGACACTCTC TGGGCATCCC CT - #GGGCTCCC   
 480                                                                      
- CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA AC - #TCCATAGC   
 540                                                                      
- GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG GGATATCCCC CG - #AGTTGGGT   
 600                                                                      
- CCCACCTTGG ACACACTGCA GCTGGACGTC GCCGACTTTG CCACCACCAT CT - #GGCAGCAG   
 660                                                                      
- ATGGAAGAAC TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GC - #CGGCCTTC   
 720                                                                      
- GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GC - #AGAGCTTC   
 780                                                                      
- CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCGACATGGC TA - #CACCATTA   
 840                                                                      
- GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA AG - #TGAGGAAG   
 900                                                                      
- ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG CCACCTACAA GC - #TGTGCCAC   
 960                                                                      
#   975                                                                   
- (2) INFORMATION FOR SEQ ID NO:264:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 975 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:264:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC CC - #TGCAGCTG   
 480                                                                      
- GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT ACCAGGGGCT CC - #TGCAGGCC   
 540                                                                      
- CTGGAAGGGA TATCCCCCGA GTTGGGTCCC ACCTTGGACA CACTGCAGCT GG - #ACGTCGCC   
 600                                                                      
- GACTTTGCCA CCACCATCTG GCAGCAGATG GAAGAACTGG GAATGGCCCC TG - #CCCTGCAG   
 660                                                                      
- CCCACCCAGG GTGCCATGCC GGCCTTCGCC TCTGCTTTCC AGCGCCGGGC AG - #GAGGGGTC   
 720                                                                      
- CTGGTTGCTA GCCATCTGCA GAGCTTCCTG GAGGTGTCGT ACCGCGTTCT AC - #GCCACCTT   
 780                                                                      
- GCGCAGCCCG ACATGGCTAC ACCATTAGGC CCTGCCAGCT CCCTGCCCCA GA - #GCTTCCTG   
 840                                                                      
- CTCAAGTCTT TAGAGCAAGT GAGGAAGATC CAGGGCGATG GCGCAGCGCT CC - #AGGAGAAG   
 900                                                                      
- CTGTGTGCCA CCTACAAGCT GTGCCACCCC GAGGAGCTGG TGCTGCTCGG AC - #ACTCTCTG   
 960                                                                      
#   975                                                                   
- (2) INFORMATION FOR SEQ ID NO:265:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 975 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:265:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTCAGGCC CTGCAGCTGG CAGGCTGCTT GA - #GCCAACTC   
 480                                                                      
- CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT AT - #CCCCCGAG   
 540                                                                      
- TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CA - #CCATCTGG   
 600                                                                      
- CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TG - #CCATGCCG   
 660                                                                      
- GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CC - #ATCTGCAG   
 720                                                                      
- AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCGA CA - #TGGCTACA   
 780                                                                      
- CCATTAGGCC CTGCCAGCTC CCTGCCCCAG AGCTTCCTGC TCAAGTCTTT AG - #AGCAAGTG   
 840                                                                      
- AGGAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CT - #ACAAGCTG   
 900                                                                      
- TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GG - #CTCCCCTG   
 960                                                                      
#   975                                                                   
- (2) INFORMATION FOR SEQ ID NO:266:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 975 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:266:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTCTGCAG CTGGCAGGCT GCTTGAGCCA AC - #TCCATAGC   
 480                                                                      
- GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG GGATATCCCC CG - #AGTTGGGT   
 540                                                                      
- CCCACCTTGG ACACACTGCA GCTGGACGTC GCCGACTTTG CCACCACCAT CT - #GGCAGCAG   
 600                                                                      
- ATGGAAGAAC TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GC - #CGGCCTTC   
 660                                                                      
- GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GC - #AGAGCTTC   
 720                                                                      
- CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCGACATGGC TA - #CACCATTA   
 780                                                                      
- GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA AG - #TGAGGAAG   
 840                                                                      
- ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG CCACCTACAA GC - #TGTGCCAC   
 900                                                                      
- CCCGAGGAGC TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CC - #TGAGCTCC   
 960                                                                      
#   975                                                                   
- (2) INFORMATION FOR SEQ ID NO:267:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 975 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:267:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTCTGGCA GGCTGCTTGA GCCAACTCCA TA - #GCGGCCTT   
 480                                                                      
- TTCCTCTACC AGGGGCTCCT GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GG - #GTCCCACC   
 540                                                                      
- TTGGACACAC TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCA GC - #AGATGGAA   
 600                                                                      
- GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CT - #TCGCCTCT   
 660                                                                      
- GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC ATCTGCAGAG CT - #TCCTGGAG   
 720                                                                      
- GTGTCGTACC GCGTTCTACG CCACCTTGCG CAGCCCGACA TGGCTACACC AT - #TAGGCCCT   
 780                                                                      
- GCCAGCTCCC TGCCCCAGAG CTTCCTGCTC AAGTCTTTAG AGCAAGTGAG GA - #AGATCCAG   
 840                                                                      
- GGCGATGGCG CAGCGCTCCA GGAGAAGCTG TGTGCCACCT ACAAGCTGTG CC - #ACCCCGAG   
 900                                                                      
- GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG CTCCCCTGAG CT - #CCTGCCCC   
 960                                                                      
#   975                                                                   
- (2) INFORMATION FOR SEQ ID NO:268:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 975 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: single                                        
          (D) TOPOLOGY: linear                                            
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:268:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTGAACTG GGAATGGCCC CTGCCCTGCA GC - #CCACCCAG   
 480                                                                      
- GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT CC - #TGGTTGCT   
 540                                                                      
- AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC TACGCCACCT TG - #CGCAGCCC   
 600                                                                      
- GACATGGCTA CACCATTAGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GC - #TCAAGTCT   
 660                                                                      
- TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA GC - #TGTGTGCC   
 720                                                                      
- ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG GACACTCTCT GG - #GCATCCCC   
 780                                                                      
- TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CT - #TGAGCCAA   
 840                                                                      
- CTCCATAGCG GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GA - #TATCCCCC   
 900                                                                      
- GAGTTGGGTC CCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CA - #CCACCATC   
 960                                                                      
#   975                                                                   
- (2) INFORMATION FOR SEQ ID NO:269:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 975 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:269:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTGGAATG GCCCCTGCCC TGCAGCCCAC CC - #AGGGTGCC   
 480                                                                      
- ATGCCGGCCT TCGCCTCTGC TTTCCAGCGC CGGGCAGGAG GGGTCCTGGT TG - #CTAGCCAT   
 540                                                                      
- CTGCAGAGCT TCCTGGAGGT GTCGTACCGC GTTCTACGCC ACCTTGCGCA GC - #CCGACATG   
 600                                                                      
- GCTACACCAT TAGGCCCTGC CAGCTCCCTG CCCCAGAGCT TCCTGCTCAA GT - #CTTTAGAG   
 660                                                                      
- CAAGTGAGGA AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TG - #CCACCTAC   
 720                                                                      
- AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CC - #CCTGGGCT   
 780                                                                      
- CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG CC - #AACTCCAT   
 840                                                                      
- AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG AAGGGATATC CC - #CCGAGTTG   
 900                                                                      
- GGTCCCACCT TGGACACACT GCAGCTGGAC GTCGCCGACT TTGCCACCAC CA - #TCTGGCAG   
 960                                                                      
#   975                                                                   
- (2) INFORMATION FOR SEQ ID NO:270:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 975 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:270:                           
- ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG AC - #CACCTGCA   
  60                                                                      
- CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GG - #ATCGAAAC   
 120                                                                      
- CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AA - #ATGCATCA   
 180                                                                      
- GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GG - #CCGCACCC   
 240                                                                      
- TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AA - #AACTGACG   
 300                                                                      
- TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CG - #GTGGAGGC   
 360                                                                      
- TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GT - #CTAAAGAA   
 420                                                                      
- TCTCATAAAT CTCCAAACAT GGCTAGCTTC CTGGAGGTGT CGTACCGCGT TC - #TACGCCAC   
 480                                                                      
- CTTGCGCAGC CCGACATGGC TACACCATTA GGCCCTGCCA GCTCCCTGCC CC - #AGAGCTTC   
 540                                                                      
- CTGCTCAAGT CTTTAGAGCA AGTGAGGAAG ATCCAGGGCG ATGGCGCAGC GC - #TCCAGGAG   
 600                                                                      
- AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CG - #GACACTCT   
 660                                                                      
- CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA GC - #TGGCAGGC   
 720                                                                      
- TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GG - #CCCTGGAA   
 780                                                                      
- GGGATATCCC CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CG - #CCGACTTT   
 840                                                                      
- GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT GC - #AGCCCACC   
 900                                                                      
- CAGGGTGCCA TGCCGGCCTT CGCCTCTGCT TTCCAGCGCC GGGCAGGAGG GG - #TCCTGGTT   
 960                                                                      
#   975                                                                   
- (2) INFORMATION FOR SEQ ID NO:271:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 325 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:271:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Leu Gly Pro Ala Ser Ser Le - #u Pro Gln Ser Phe Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gl - #n Gly Asp Gly Ala Ala     
#               175                                                       
- Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Le - #u Cys His Pro Glu Glu     
#           190                                                           
- Leu Val Leu Leu Gly His Ser Leu Gly Ile Pr - #o Trp Ala Pro Leu Ser     
#       205                                                               
- Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gl - #y Cys Leu Ser Gln Leu     
#   220                                                                   
- His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Le - #u Gln Ala Leu Glu Gly     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Th - #r Leu Gln Leu Asp Val     
#               255                                                       
- Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Me - #t Glu Glu Leu Gly Met     
#           270                                                           
- Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Me - #t Pro Ala Phe Ala Ser     
#       285                                                               
- Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Va - #l Ala Ser His Leu Gln     
#   300                                                                   
- Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Ar - #g His Leu Ala Gln Pro     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Asp Met Ala Thr Pro                                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:272:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 325 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:272:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Leu Gly Pro Ala Ser Ser Le - #u Pro Gln Ser Phe Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gl - #n Gly Asp Gly Ala Ala     
#               175                                                       
- Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Le - #u Cys His Pro Glu Glu     
#           190                                                           
- Leu Val Leu Leu Gly His Ser Leu Gly Ile Pr - #o Trp Ala Pro Leu Ser     
#       205                                                               
- Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gl - #y Cys Leu Ser Gln Leu     
#   220                                                                   
- His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Le - #u Gln Ala Leu Glu Gly     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Th - #r Leu Gln Leu Asp Val     
#               255                                                       
- Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Me - #t Glu Glu Leu Gly Met     
#           270                                                           
- Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Me - #t Pro Ala Phe Ala Ser     
#       285                                                               
- Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Va - #l Ala Ser His Leu Gln     
#   300                                                                   
- Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Ar - #g His Leu Ala Gln Pro     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Asp Met Ala Thr Pro                                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:273:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 325 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:273:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Phe Leu Leu Lys Ser Leu Gl - #u Gln Val Arg Lys Ile     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Le - #u Cys Ala Thr Tyr Lys     
#               175                                                       
- Leu Cys His Pro Glu Glu Leu Val Leu Leu Gl - #y His Ser Leu Gly Ile     
#           190                                                           
- Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gl - #n Ala Leu Gln Leu Ala     
#       205                                                               
- Gly Cys Leu Ser Gln Leu His Ser Gly Leu Ph - #e Leu Tyr Gln Gly Leu     
#   220                                                                   
- Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Le - #u Gly Pro Thr Leu Asp     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Th - #r Thr Ile Trp Gln Gln     
#               255                                                       
- Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gl - #n Pro Thr Gln Gly Ala     
#           270                                                           
- Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Ar - #g Ala Gly Gly Val Leu     
#       285                                                               
- Val Ala Ser His Leu Gln Ser Phe Leu Glu Va - #l Ser Tyr Arg Val Leu     
#   300                                                                   
- Arg His Leu Ala Gln Pro Asp Met Ala Thr Pr - #o Leu Gly Pro Ala Ser     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Ser Leu Pro Gln Ser                                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:274:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 325 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:274:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Glu Gln Val Arg Lys Ile Gl - #n Gly Asp Gly Ala Ala     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Le - #u Cys His Pro Glu Glu     
#               175                                                       
- Leu Val Leu Leu Gly His Ser Leu Gly Ile Pr - #o Trp Ala Pro Leu Ser     
#           190                                                           
- Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gl - #y Cys Leu Ser Gln Leu     
#       205                                                               
- His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Le - #u Gln Ala Leu Glu Gly     
#   220                                                                   
- Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Th - #r Leu Gln Leu Asp Val     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Me - #t Glu Glu Leu Gly Met     
#               255                                                       
- Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Me - #t Pro Ala Phe Ala Ser     
#           270                                                           
- Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Va - #l Ala Ser His Leu Gln     
#       285                                                               
- Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Ar - #g His Leu Ala Gln Pro     
#   300                                                                   
- Asp Met Ala Thr Pro Leu Gly Pro Ala Ser Se - #r Leu Pro Gln Ser Phe     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Leu Leu Lys Ser Leu                                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:275:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 325 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:275:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Leu Leu Gly His Ser Leu Gl - #y Ile Pro Trp Ala Pro     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Le - #u Ala Gly Cys Leu Ser     
#               175                                                       
- Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gl - #y Leu Leu Gln Ala Leu     
#           190                                                           
- Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Le - #u Asp Thr Leu Gln Leu     
#       205                                                               
- Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gl - #n Gln Met Glu Glu Leu     
#   220                                                                   
- Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gl - #y Ala Met Pro Ala Phe     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Va - #l Leu Val Ala Ser His     
#               255                                                       
- Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Va - #l Leu Arg His Leu Ala     
#           270                                                           
- Gln Pro Asp Met Ala Thr Pro Leu Gly Pro Al - #a Ser Ser Leu Pro Gln     
#       285                                                               
- Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Ar - #g Lys Ile Gln Gly Asp     
#   300                                                                   
- Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Th - #r Tyr Lys Leu Cys His     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Pro Glu Glu Leu Val                                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:276:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 325 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:276:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Pro Leu Ser Ser Cys Pro Se - #r Gln Ala Leu Gln Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ala Gly Cys Leu Ser Gln Leu His Ser Gly Le - #u Phe Leu Tyr Gln Gly     
#               175                                                       
- Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Gl - #u Leu Gly Pro Thr Leu     
#           190                                                           
- Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Al - #a Thr Thr Ile Trp Gln     
#       205                                                               
- Gln Met Glu Glu Leu Gly Met Ala Pro Ala Le - #u Gln Pro Thr Gln Gly     
#   220                                                                   
- Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Ar - #g Arg Ala Gly Gly Val     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Val Ala Ser His Leu Gln Ser Phe Leu Gl - #u Val Ser Tyr Arg Val     
#               255                                                       
- Leu Arg His Leu Ala Gln Pro Asp Met Ala Th - #r Pro Leu Gly Pro Ala     
#           270                                                           
- Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Se - #r Leu Glu Gln Val Arg     
#       285                                                               
- Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Gl - #u Lys Leu Cys Ala Thr     
#   300                                                                   
- Tyr Lys Leu Cys His Pro Glu Glu Leu Val Le - #u Leu Gly His Ser Leu     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Gly Ile Pro Trp Ala                                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:277:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 325 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:277:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Gln Ala Leu Gln Leu Ala Gl - #y Cys Leu Ser Gln Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Le - #u Gln Ala Leu Glu Gly     
#               175                                                       
- Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Th - #r Leu Gln Leu Asp Val     
#           190                                                           
- Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Me - #t Glu Glu Leu Gly Met     
#       205                                                               
- Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Me - #t Pro Ala Phe Ala Ser     
#   220                                                                   
- Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Va - #l Ala Ser His Leu Gln     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Ar - #g His Leu Ala Gln Pro     
#               255                                                       
- Asp Met Ala Thr Pro Leu Gly Pro Ala Ser Se - #r Leu Pro Gln Ser Phe     
#           270                                                           
- Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Il - #e Gln Gly Asp Gly Ala     
#       285                                                               
- Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Ly - #s Leu Cys His Pro Glu     
#   300                                                                   
- Glu Leu Val Leu Leu Gly His Ser Leu Gly Il - #e Pro Trp Ala Pro Leu     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Ser Ser Cys Pro Ser                                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:278:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 325 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:278:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Leu Gln Leu Ala Gly Cys Le - #u Ser Gln Leu His Ser     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Al - #a Leu Glu Gly Ile Ser     
#               175                                                       
- Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gl - #n Leu Asp Val Ala Asp     
#           190                                                           
- Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Gl - #u Leu Gly Met Ala Pro     
#       205                                                               
- Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Al - #a Phe Ala Ser Ala Phe     
#   220                                                                   
- Gln Arg Arg Ala Gly Gly Val Leu Val Ala Se - #r His Leu Gln Ser Phe     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Leu Glu Val Ser Tyr Arg Val Leu Arg His Le - #u Ala Gln Pro Asp Met     
#               255                                                       
- Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pr - #o Gln Ser Phe Leu Leu     
#           270                                                           
- Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gl - #y Asp Gly Ala Ala Leu     
#       285                                                               
- Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cy - #s His Pro Glu Glu Leu     
#   300                                                                   
- Val Leu Leu Gly His Ser Leu Gly Ile Pro Tr - #p Ala Pro Leu Ser Ser     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Cys Pro Ser Gln Ala                                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:279:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 325 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:279:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Leu Ala Gly Cys Leu Ser Gl - #n Leu His Ser Gly Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Gl - #u Gly Ile Ser Pro Glu     
#               175                                                       
- Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu As - #p Val Ala Asp Phe Ala     
#           190                                                           
- Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gl - #y Met Ala Pro Ala Leu     
#       205                                                               
- Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Al - #a Ser Ala Phe Gln Arg     
#   220                                                                   
- Arg Ala Gly Gly Val Leu Val Ala Ser His Le - #u Gln Ser Phe Leu Glu     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Val Ser Tyr Arg Val Leu Arg His Leu Ala Gl - #n Pro Asp Met Ala Thr     
#               255                                                       
- Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Se - #r Phe Leu Leu Lys Ser     
#           270                                                           
- Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gl - #y Ala Ala Leu Gln Glu     
#       285                                                               
- Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pr - #o Glu Glu Leu Val Leu     
#   300                                                                   
- Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pr - #o Leu Ser Ser Cys Pro     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Ser Gln Ala Leu Gln                                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:280:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 325 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:280:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Glu Leu Gly Met Ala Pro Al - #a Leu Gln Pro Thr Gln     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gl - #n Arg Arg Ala Gly Gly     
#               175                                                       
- Val Leu Val Ala Ser His Leu Gln Ser Phe Le - #u Glu Val Ser Tyr Arg     
#           190                                                           
- Val Leu Arg His Leu Ala Gln Pro Asp Met Al - #a Thr Pro Leu Gly Pro     
#       205                                                               
- Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Ly - #s Ser Leu Glu Gln Val     
#   220                                                                   
- Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gl - #n Glu Lys Leu Cys Ala     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Va - #l Leu Leu Gly His Ser     
#               255                                                       
- Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cy - #s Pro Ser Gln Ala Leu     
#           270                                                           
- Gln Leu Ala Gly Cys Leu Ser Gln Leu His Se - #r Gly Leu Phe Leu Tyr     
#       285                                                               
- Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Se - #r Pro Glu Leu Gly Pro     
#   300                                                                   
- Thr Leu Asp Thr Leu Gln Leu Asp Val Ala As - #p Phe Ala Thr Thr Ile     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Trp Gln Gln Met Glu                                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:281:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 325 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:281:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Gly Met Ala Pro Ala Leu Gl - #n Pro Thr Gln Gly Ala     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Ar - #g Ala Gly Gly Val Leu     
#               175                                                       
- Val Ala Ser His Leu Gln Ser Phe Leu Glu Va - #l Ser Tyr Arg Val Leu     
#           190                                                           
- Arg His Leu Ala Gln Pro Asp Met Ala Thr Pr - #o Leu Gly Pro Ala Ser     
#       205                                                               
- Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Le - #u Glu Gln Val Arg Lys     
#   220                                                                   
- Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Ly - #s Leu Cys Ala Thr Tyr     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Lys Leu Cys His Pro Glu Glu Leu Val Leu Le - #u Gly His Ser Leu Gly     
#               255                                                       
- Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Se - #r Gln Ala Leu Gln Leu     
#           270                                                           
- Ala Gly Cys Leu Ser Gln Leu His Ser Gly Le - #u Phe Leu Tyr Gln Gly     
#       285                                                               
- Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Gl - #u Leu Gly Pro Thr Leu     
#   300                                                                   
- Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Al - #a Thr Thr Ile Trp Gln     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Gln Met Glu Glu Leu                                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:282:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 325 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:282:                           
- Met Ala Asn Cys Ser Ile Met Ile Asp Glu Il - #e Ile His His Leu Lys     
#                15                                                       
- Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn As - #n Leu Asn Asp Glu Asp     
#            30                                                           
- Val Ser Ile Leu Met Asp Arg Asn Leu Arg Le - #u Pro Asn Leu Glu Ser     
#        45                                                               
- Phe Val Arg Ala Val Lys Asn Leu Glu Asn Al - #a Ser Gly Ile Glu Ala     
#    60                                                                   
- Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Se - #r Ala Thr Ala Ala Pro     
#80                                                                       
- Ser Arg His Pro Ile Ile Ile Lys Ala Gly As - #p Trp Gln Glu Phe Arg     
#                95                                                       
- Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Gl - #u Gln Ala Gln Glu Gln     
#           110                                                           
- Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gl - #y Glu Pro Ser Gly Pro     
#       125                                                               
- Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Ly - #s Glu Ser His Lys Ser     
#   140                                                                   
- Pro Asn Met Ala Ser Phe Leu Glu Val Ser Ty - #r Arg Val Leu Arg His     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Leu Ala Gln Pro Asp Met Ala Thr Pro Leu Gl - #y Pro Ala Ser Ser Leu     
#               175                                                       
- Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gl - #n Val Arg Lys Ile Gln     
#           190                                                           
- Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cy - #s Ala Thr Tyr Lys Leu     
#       205                                                               
- Cys His Pro Glu Glu Leu Val Leu Leu Gly Hi - #s Ser Leu Gly Ile Pro     
#   220                                                                   
- Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Al - #a Leu Gln Leu Ala Gly     
225                 2 - #30                 2 - #35                 2 -   
#40                                                                       
- Cys Leu Ser Gln Leu His Ser Gly Leu Phe Le - #u Tyr Gln Gly Leu Leu     
#               255                                                       
- Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gl - #y Pro Thr Leu Asp Thr     
#           270                                                           
- Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Th - #r Ile Trp Gln Gln Met     
#       285                                                               
- Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pr - #o Thr Gln Gly Ala Met     
#   300                                                                   
- Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Al - #a Gly Gly Val Leu Val     
305                 3 - #10                 3 - #15                 3 -   
#20                                                                       
- Ala Ser His Leu Gln                                                     
                325                                                       
- (2) INFORMATION FOR SEQ ID NO:283:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 153 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 7                                                 
#/note= "Xaa at position 7 is Ser or                                      
               Ala;"                                                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 112                                               
#/note= "Xaa at position 112 is:                                          
               deleted o - #r Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met;  
- #"                                                                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 113                                               
#/note= "Xaa at position 113 is:                                          
               deleted o - #r Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;  
- #"                                                                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 114                                               
#/note= "Xaa at position 114 is:                                          
               deleted o - #r Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;  
- #"                                                                      
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 115                                               
#/note= "Xaa at position 115 is:                                          
               deleted o - #r Gln, Gly, Ser, Thr, Tyr, or Asn;"           
-     (ix) FEATURE:                                                       
          (A) NAME/KEY: Modified-sit - #e                                 
          (B) LOCATION: 151                                               
#/note= "Xaa at position 151 is Ser                                       
               or Ala;"                                                   
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:283:                           
- Ser Pro Ala Pro Pro Ala Xaa Asp Leu Arg Va - #l Leu Ser Lys Leu Leu     
#                15                                                       
- Arg Asp Ser His Val Leu His Ser Arg Leu Se - #r Gln Cys Pro Glu Val     
#            30                                                           
- His Pro Leu Pro Thr Pro Val Leu Leu Pro Al - #a Val Asp Phe Ser Leu     
#        45                                                               
- Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Ly - #s Ala Gln Asp Ile Leu     
#    60                                                                   
- Gly Ala Val Thr Leu Leu Leu Glu Gly Val Me - #t Ala Ala Arg Gly Gln     
#80                                                                       
- Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gl - #y Gln Leu Ser Gly Gln     
#                95                                                       
- Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Le - #u Leu Gly Thr Gln Xaa     
#           110                                                           
- Xaa Xaa Xaa Gly Arg Thr Thr Ala His Lys As - #p Pro Asn Ala Ile Phe     
#       125                                                               
- Leu Ser Phe Gln His Leu Leu Arg Gly Lys Va - #l Arg Phe Leu Met Leu     
#   140                                                                   
- Val Gly Gly Ser Thr Leu Xaa Val Arg                                     
145                 1 - #50                                               
- (2) INFORMATION FOR SEQ ID NO:284:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 162 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:284:                           
- Met Ala Gly Arg Thr Thr Ala His Lys Asp Pr - #o Asn Ala Ile Phe Leu     
#                15                                                       
- Ser Phe Gln His Leu Leu Arg Gly Lys Val Ar - #g Phe Leu Met Leu Val     
#            30                                                           
- Gly Gly Ser Thr Leu Ala Val Arg Glu Phe Gl - #y Gly Asn Met Ala Ser     
#        45                                                               
- Pro Ala Pro Pro Ala Ala Asp Leu Arg Val Le - #u Ser Lys Leu Leu Arg     
#    60                                                                   
- Asp Ser His Val Leu His Ser Arg Leu Ser Gl - #n Cys Pro Glu Val His     
#80                                                                       
- Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Va - #l Asp Phe Ser Leu Gly     
#                95                                                       
- Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Al - #a Gln Asp Ile Leu Gly     
#           110                                                           
- Ala Val Thr Leu Leu Leu Glu Gly Val Met Al - #a Ala Arg Gly Gln Leu     
#       125                                                               
- Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gl - #n Leu Ser Gly Gln Val     
#   140                                                                   
- Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Le - #u Gly Thr Gln Leu Pro     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Pro Gln                                                                 
- (2) INFORMATION FOR SEQ ID NO:285:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 162 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:285:                           
- Met Ala Gly Pro Thr Cys Leu Ser Ser Leu Le - #u Gly Gln Leu Ser Gly     
#                15                                                       
- Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Se - #r Leu Leu Gly Thr Gln     
#            30                                                           
- Leu Pro Pro Gln Gly Arg Thr Thr Ala His Ly - #s Asp Pro Asn Ala Ile     
#        45                                                               
- Phe Leu Ser Phe Gln His Leu Leu Arg Gly Ly - #s Val Arg Phe Leu Met     
#    60                                                                   
- Leu Val Gly Gly Ser Thr Leu Ala Val Arg Gl - #u Phe Gly Gly Asn Met     
#80                                                                       
- Ala Ser Pro Ala Pro Pro Ala Ala Asp Leu Ar - #g Val Leu Ser Lys Leu     
#                95                                                       
- Leu Arg Asp Ser His Val Leu His Ser Arg Le - #u Ser Gln Cys Pro Glu     
#           110                                                           
- Val His Pro Leu Pro Thr Pro Val Leu Leu Pr - #o Ala Val Asp Phe Ser     
#       125                                                               
- Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Th - #r Lys Ala Gln Asp Ile     
#   140                                                                   
- Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Va - #l Met Ala Ala Arg Gly     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gln Leu                                                                 
- (2) INFORMATION FOR SEQ ID NO:286:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 180 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
               "                                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:286:                           
- Ala Thr Gly Gly Cys Thr Gly Gly Ala Cys Cy - #s Cys Ala Cys Thr Thr     
#                15                                                       
- Gly Cys Cys Thr Cys Thr Cys Ala Thr Cys Cy - #s Cys Thr Cys Cys Thr     
#            30                                                           
- Gly Gly Gly Gly Cys Ala Gly Cys Thr Thr Th - #r Cys Thr Gly Gly Ala     
#        45                                                               
- Cys Ala Gly Gly Thr Cys Cys Gly Thr Cys Th - #r Cys Cys Thr Cys Cys     
#    60                                                                   
- Thr Thr Gly Gly Gly Gly Cys Cys Cys Thr Gl - #y Cys Ala Gly Ala Gly     
#80                                                                       
- Cys Cys Thr Cys Cys Thr Thr Gly Gly Ala Al - #a Cys Cys Cys Ala Gly     
#                95                                                       
- Cys Thr Thr Cys Cys Thr Cys Cys Ala Cys Al - #a Gly Gly Gly Cys Ala     
#           110                                                           
- Gly Gly Ala Cys Cys Ala Cys Ala Gly Cys Th - #r Cys Ala Cys Ala Ala     
#       125                                                               
- Gly Gly Ala Thr Cys Cys Cys Ala Ala Thr Gl - #y Cys Cys Ala Thr Cys     
#   140                                                                   
- Thr Thr Cys Cys Thr Gly Ala Gly Cys Thr Th - #r Cys Cys Ala Ala Cys     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ala Cys Cys Thr Gly Cys Thr Cys Cys Gly Al - #a Gly Gly Ala Ala Ala     
#               175                                                       
- Gly Gly Thr Gly                                                         
            180                                                           
- (2) INFORMATION FOR SEQ ID NO:287:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 486 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:287:                           
- ATGGCTGGCA GGACCACAGC TCACAAGGAT CCCAATGCCA TCTTCCTGAG CT - #TCCAACAC   
  60                                                                      
- CTGCTCCGAG GAAAGGTGCG TTTCCTGATG CTTGTAGGAG GGTCCACCCT CG - #CCGTCAGG   
 120                                                                      
- GAATTCGGCG GCAACATGGC GTCTCCGGCG CCGCCTGCTG CTGACCTCCG AG - #TCCTCAGT   
 180                                                                      
- AAACTGCTTC GTGACTCCCA TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AG - #AGGTTCAC   
 240                                                                      
- CCTTTGCCTA CACCTGTCCT GCTGCCTGCT GTGGACTTTA GCTTGGGAGA AT - #GGAAAACC   
 300                                                                      
- CAGATGGAGG AGACCAAGGC ACAGGACATT CTGGGAGCAG TGACCCTTCT GC - #TGGAGGGA   
 360                                                                      
- GTGATGGCAG CACGGGGACA ACTGGGACCC ACTTGCCTCT CATCCCTCCT GG - #GGCAGCTT   
 420                                                                      
- TCTGGACAGG TCCGTCTCCT CCTTGGGGCC CTGCAGAGCC TCCTTGGAAC CC - #AGCTTCCT   
 480                                                                      
#          486                                                            
- (2) INFORMATION FOR SEQ ID NO:288:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 531 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:288:                           
- CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGGAAGA TCCAGGGCGA TG - #GCGCAGCG   
  60                                                                      
- CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC CCGAGGAGCT GG - #TGCTGCTC   
 120                                                                      
- GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GG - #CCCTGCAG   
 180                                                                      
- CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GC - #TCCTGCAG   
 240                                                                      
- GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GC - #TGGACGTC   
 300                                                                      
- GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CC - #CTGCCCTG   
 360                                                                      
- CAGCCCACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GG - #CAGGAGGG   
 420                                                                      
- GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TC - #TACGCCAC   
 480                                                                      
#            531ACATGGC TACACCATTA GGCCCTGCCA GCTCCCTGCC C                
- (2) INFORMATION FOR SEQ ID NO:289:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 531 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:289:                           
- GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CT - #TCGCCTCT   
  60                                                                      
- GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC ATCTGCAGAG CT - #TCCTGGAG   
 120                                                                      
- GTGTCGTACC GCGTTCTACG CCACCTTGCG CAGCCCGACA TGGCTACACC AT - #TAGGCCCT   
 180                                                                      
- GCCAGCTCCC TGCCCCAGAG CTTCCTGCTC AAGTCTTTAG AGCAAGTGAG GA - #AGATCCAG   
 240                                                                      
- GGCGATGGCG CAGCGCTCCA GGAGAAGCTG TGTGCCACCT ACAAGCTGTG CC - #ACCCCGAG   
 300                                                                      
- GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG CTCCCCTGAG CT - #CCTGCCCC   
 360                                                                      
- AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TT - #TCCTCTAC   
 420                                                                      
- CAGGGGCTCC TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CT - #TGGACACA   
 480                                                                      
#            531TCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA A                
- (2) INFORMATION FOR SEQ ID NO:290:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 531 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:290:                           
- GGAATGGCCC CTGCCCTGCA GCCCACCCAG GGTGCCATGC CGGCCTTCGC CT - #CTGCTTTC   
  60                                                                      
- CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GG - #AGGTGTCG   
 120                                                                      
- TACCGCGTTC TACGCCACCT TGCGCAGCCC GACATGGCTA CACCATTAGG CC - #CTGCCAGC   
 180                                                                      
- TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG TGAGGAAGAT CC - #AGGGCGAT   
 240                                                                      
- GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC CG - #AGGAGCTG   
 300                                                                      
- GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CC - #CCAGCCAG   
 360                                                                      
- GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CT - #ACCAGGGG   
 420                                                                      
- CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC CCACCTTGGA CA - #CACTGCAG   
 480                                                                      
#            531ACTTTGC CACCACCATC TGGCAGCAGA TGGAAGAACT G                
- (2) INFORMATION FOR SEQ ID NO:291:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 531 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:291:                           
- TTCCTGCTCA AGTCTTTAGA GCAAGTGAGG AAGATCCAGG GCGATGGCGC AG - #CGCTCCAG   
  60                                                                      
- GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GC - #TCGGACAC   
 120                                                                      
- TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GC - #AGCTGGCA   
 180                                                                      
- GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GC - #AGGCCCTG   
 240                                                                      
- GAAGGGATAT CCCCCGAGTT GGGTCCCACC TTGGACACAC TGCAGCTGGA CG - #TCGCCGAC   
 300                                                                      
- TTTGCCACCA CCATCTGGCA GCAGATGGAA GAACTGGGAA TGGCCCCTGC CC - #TGCAGCCC   
 360                                                                      
- ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AG - #GGGTCCTG   
 420                                                                      
- GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CC - #ACCTTGCG   
 480                                                                      
#            531CTACACC ATTAGGCCCT GCCAGCTCCC TGCCCCAGAG C                
- (2) INFORMATION FOR SEQ ID NO:292:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 531 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:292:                           
- AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCGA CA - #TGGCTACA   
  60                                                                      
- CCATTAGGCC CTGCCAGCTC CCTGCCCCAG AGCTTCCTGC TCAAGTCTTT AG - #AGCAAGTG   
 120                                                                      
- AGGAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CT - #ACAAGCTG   
 180                                                                      
- TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GG - #CTCCCCTG   
 240                                                                      
- AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CC - #ATAGCGGC   
 300                                                                      
- CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GT - #TGGGTCCC   
 360                                                                      
- ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GC - #AGCAGATG   
 420                                                                      
- GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCACCCAGG GTGCCATGCC GG - #CCTTCGCC   
 480                                                                      
#            531GCCGGGC AGGAGGGGTC CTGGTTGCTA GCCATCTGCA G                
- (2) INFORMATION FOR SEQ ID NO:293:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 531 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:293:                           
- AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCGA CA - #TGGCTACA   
  60                                                                      
- CCATTAGGCC CTGCCAGCTC CCTGCCCCAG AGCTTCCTGC TCAAGTCTTT AG - #AGCAAGTG   
 120                                                                      
- AGGAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CT - #ACAAGCTG   
 180                                                                      
- TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GG - #CTCCCCTG   
 240                                                                      
- AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CC - #ATAGCGGC   
 300                                                                      
- CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GT - #TGGGTCCC   
 360                                                                      
- ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GC - #AGCAGATG   
 420                                                                      
- GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCACCCAGG GTGCCATGCC GG - #CCTTCGCC   
 480                                                                      
#            531GCCGGGC AGGAGGGGTC CTGGTTGCTA GCCATCTGCA G                
- (2) INFORMATION FOR SEQ ID NO:294:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 531 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:294:                           
- TTAGGCCCTG CCAGCTCCCT GCCCCAGAGC TTCCTGCTCA AGTCTTTAGA GC - #AAGTGAGG   
  60                                                                      
- AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CA - #AGCTGTGC   
 120                                                                      
- CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC TC - #CCCTGAGC   
 180                                                                      
- TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA GCCAACTCCA TA - #GCGGCCTT   
 240                                                                      
- TTCCTCTACC AGGGGCTCCT GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GG - #GTCCCACC   
 300                                                                      
- TTGGACACAC TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCA GC - #AGATGGAA   
 360                                                                      
- GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CT - #TCGCCTCT   
 420                                                                      
- GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC ATCTGCAGAG CT - #TCCTGGAG   
 480                                                                      
#            531TTCTACG CCACCTTGCG CAGCCCGACA TGGCTACACC A                
- (2) INFORMATION FOR SEQ ID NO:295:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 531 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:295:                           
- CTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCC CA - #GCCAGGCC   
  60                                                                      
- CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCC TTTTCCTCTA CC - #AGGGGCTC   
 120                                                                      
- CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG TTGGGTCCCA CCTTGGACAC AC - #TGCAGCTG   
 180                                                                      
- GACGTCGCCG ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AA - #TGGCCCCT   
 240                                                                      
- GCCCTGCAGC CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GC - #GCCGGGCA   
 300                                                                      
- GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CC - #GCGTTCTA   
 360                                                                      
- CGCCACCTTG CGCAGCCCGA CATGGCTACA CCATTAGGCC CTGCCAGCTC CC - #TGCCCCAG   
 420                                                                      
- AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG AGGAAGATCC AGGGCGATGG CG - #CAGCGCTC   
 480                                                                      
#            531GTGCCAC CTACAAGCTG TGCCACCCCG AGGAGCTGGT G                
- (2) INFORMATION FOR SEQ ID NO:296:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 531 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:296:                           
- CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG CC - #AACTCCAT   
  60                                                                      
- AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG AAGGGATATC CC - #CCGAGTTG   
 120                                                                      
- GGTCCCACCT TGGACACACT GCAGCTGGAC GTCGCCGACT TTGCCACCAC CA - #TCTGGCAG   
 180                                                                      
- CAGATGGAAG AACTGGGAAT GGCCCCTGCC CTGCAGCCCA CCCAGGGTGC CA - #TGCCGGCC   
 240                                                                      
- TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA GGGGTCCTGG TTGCTAGCCA TC - #TGCAGAGC   
 300                                                                      
- TTCCTGGAGG TGTCGTACCG CGTTCTACGC CACCTTGCGC AGCCCGACAT GG - #CTACACCA   
 360                                                                      
- TTAGGCCCTG CCAGCTCCCT GCCCCAGAGC TTCCTGCTCA AGTCTTTAGA GC - #AAGTGAGG   
 420                                                                      
- AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CA - #AGCTGTGC   
 480                                                                      
#            531TGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC T                
- (2) INFORMATION FOR SEQ ID NO:297:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 531 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:297:                           
- CAGGCCCTGC AGCTGGCAGG CTGCTTGAGC CAACTCCATA GCGGCCTTTT CC - #TCTACCAG   
  60                                                                      
- GGGCTCCTGC AGGCCCTGGA AGGGATATCC CCCGAGTTGG GTCCCACCTT GG - #ACACACTG   
 120                                                                      
- CAGCTGGACG TCGCCGACTT TGCCACCACC ATCTGGCAGC AGATGGAAGA AC - #TGGGAATG   
 180                                                                      
- GCCCCTGCCC TGCAGCCCAC CCAGGGTGCC ATGCCGGCCT TCGCCTCTGC TT - #TCCAGCGC   
 240                                                                      
- CGGGCAGGAG GGGTCCTGGT TGCTAGCCAT CTGCAGAGCT TCCTGGAGGT GT - #CGTACCGC   
 300                                                                      
- GTTCTACGCC ACCTTGCGCA GCCCGACATG GCTACACCAT TAGGCCCTGC CA - #GCTCCCTG   
 360                                                                      
- CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGGA AGATCCAGGG CG - #ATGGCGCA   
 420                                                                      
- GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GC - #TGGTGCTG   
 480                                                                      
#            531TGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG C                
- (2) INFORMATION FOR SEQ ID NO:298:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 531 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:298:                           
- CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCC TTTTCCTCTA CC - #AGGGGCTC   
  60                                                                      
- CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG TTGGGTCCCA CCTTGGACAC AC - #TGCAGCTG   
 120                                                                      
- GACGTCGCCG ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AA - #TGGCCCCT   
 180                                                                      
- GCCCTGCAGC CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GC - #GCCGGGCA   
 240                                                                      
- GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CC - #GCGTTCTA   
 300                                                                      
- CGCCACCTTG CGCAGCCCGA CATGGCTACA CCATTAGGCC CTGCCAGCTC CC - #TGCCCCAG   
 360                                                                      
- AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG AGGAAGATCC AGGGCGATGG CG - #CAGCGCTC   
 420                                                                      
- CAGGAGAAGC TGTGTGCCAC CTACAAGCTG TGCCACCCCG AGGAGCTGGT GC - #TGCTCGGA   
 480                                                                      
#            531TCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC C                
- (2) INFORMATION FOR SEQ ID NO:299:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 531 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:299:                           
- CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GC - #TCCTGCAG   
  60                                                                      
- GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GC - #TGGACGTC   
 120                                                                      
- GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CC - #CTGCCCTG   
 180                                                                      
- CAGCCCACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GG - #CAGGAGGG   
 240                                                                      
- GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TC - #TACGCCAC   
 300                                                                      
- CTTGCGCAGC CCGACATGGC TACACCATTA GGCCCTGCCA GCTCCCTGCC CC - #AGAGCTTC   
 360                                                                      
- CTGCTCAAGT CTTTAGAGCA AGTGAGGAAG ATCCAGGGCG ATGGCGCAGC GC - #TCCAGGAG   
 420                                                                      
- AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CG - #GACACTCT   
 480                                                                      
#            531GGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA G                
- (2) INFORMATION FOR SEQ ID NO:300:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 177 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:300:                           
- Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Va - #l Arg Lys Ile Gln Gly     
#                15                                                       
- Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Al - #a Thr Tyr Lys Leu Cys     
#            30                                                           
- His Pro Glu Glu Leu Val Leu Leu Gly His Se - #r Leu Gly Ile Pro Trp     
#        45                                                               
- Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Le - #u Gln Leu Ala Gly Cys     
#    60                                                                   
- Leu Ser Gln Leu His Ser Gly Leu Phe Leu Ty - #r Gln Gly Leu Leu Gln     
#80                                                                       
- Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pr - #o Thr Leu Asp Thr Leu     
#                95                                                       
- Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Il - #e Trp Gln Gln Met Glu     
#           110                                                           
- Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Th - #r Gln Gly Ala Met Pro     
#       125                                                               
- Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gl - #y Gly Val Leu Val Ala     
#   140                                                                   
- Ser His Leu Gln Ser Phe Leu Glu Val Ser Ty - #r Arg Val Leu Arg His     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Leu Ala Gln Pro Asp Met Ala Thr Pro Leu Gl - #y Pro Ala Ser Ser Leu     
#               175                                                       
- Pro                                                                     
- (2) INFORMATION FOR SEQ ID NO:301:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 177 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:301:                           
- Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Th - #r Gln Gly Ala Met Pro     
#                15                                                       
- Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gl - #y Gly Val Leu Val Ala     
#            30                                                           
- Ser His Leu Gln Ser Phe Leu Glu Val Ser Ty - #r Arg Val Leu Arg His     
#        45                                                               
- Leu Ala Gln Pro Asp Met Ala Thr Pro Leu Gl - #y Pro Ala Ser Ser Leu     
#    60                                                                   
- Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gl - #n Val Arg Lys Ile Gln     
#80                                                                       
- Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cy - #s Ala Thr Tyr Lys Leu     
#                95                                                       
- Cys His Pro Glu Glu Leu Val Leu Leu Gly Hi - #s Ser Leu Gly Ile Pro     
#           110                                                           
- Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Al - #a Leu Gln Leu Ala Gly     
#       125                                                               
- Cys Leu Ser Gln Leu His Ser Gly Leu Phe Le - #u Tyr Gln Gly Leu Leu     
#   140                                                                   
- Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gl - #y Pro Thr Leu Asp Thr     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Th - #r Ile Trp Gln Gln Met     
#               175                                                       
- Glu                                                                     
- (2) INFORMATION FOR SEQ ID NO:302:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 177 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:302:                           
- Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gl - #y Ala Met Pro Ala Phe     
#                15                                                       
- Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Va - #l Leu Val Ala Ser His     
#            30                                                           
- Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Va - #l Leu Arg His Leu Ala     
#        45                                                               
- Gln Pro Asp Met Ala Thr Pro Leu Gly Pro Al - #a Ser Ser Leu Pro Gln     
#    60                                                                   
- Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Ar - #g Lys Ile Gln Gly Asp     
#80                                                                       
- Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Th - #r Tyr Lys Leu Cys His     
#                95                                                       
- Pro Glu Glu Leu Val Leu Leu Gly His Ser Le - #u Gly Ile Pro Trp Ala     
#           110                                                           
- Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gl - #n Leu Ala Gly Cys Leu     
#       125                                                               
- Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gl - #n Gly Leu Leu Gln Ala     
#   140                                                                   
- Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Th - #r Leu Asp Thr Leu Gln     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Tr - #p Gln Gln Met Glu Glu     
#               175                                                       
- Leu                                                                     
- (2) INFORMATION FOR SEQ ID NO:303:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 177 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:303:                           
- Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Ly - #s Ile Gln Gly Asp Gly     
#                15                                                       
- Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Ty - #r Lys Leu Cys His Pro     
#            30                                                           
- Glu Glu Leu Val Leu Leu Gly His Ser Leu Gl - #y Ile Pro Trp Ala Pro     
#        45                                                               
- Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Le - #u Ala Gly Cys Leu Ser     
#    60                                                                   
- Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gl - #y Leu Leu Gln Ala Leu     
#80                                                                       
- Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Le - #u Asp Thr Leu Gln Leu     
#                95                                                       
- Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gl - #n Gln Met Glu Glu Leu     
#           110                                                           
- Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gl - #y Ala Met Pro Ala Phe     
#       125                                                               
- Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Va - #l Leu Val Ala Ser His     
#   140                                                                   
- Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Va - #l Leu Arg His Leu Ala     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gln Pro Asp Met Ala Thr Pro Leu Gly Pro Al - #a Ser Ser Leu Pro Gln     
#               175                                                       
- Ser                                                                     
- (2) INFORMATION FOR SEQ ID NO:304:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 177 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:304:                           
- Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Ar - #g His Leu Ala Gln Pro     
#                15                                                       
- Asp Met Ala Thr Pro Leu Gly Pro Ala Ser Se - #r Leu Pro Gln Ser Phe     
#            30                                                           
- Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Il - #e Gln Gly Asp Gly Ala     
#        45                                                               
- Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Ly - #s Leu Cys His Pro Glu     
#    60                                                                   
- Glu Leu Val Leu Leu Gly His Ser Leu Gly Il - #e Pro Trp Ala Pro Leu     
#80                                                                       
- Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Al - #a Gly Cys Leu Ser Gln     
#                95                                                       
- Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Le - #u Leu Gln Ala Leu Glu     
#           110                                                           
- Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu As - #p Thr Leu Gln Leu Asp     
#       125                                                               
- Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gl - #n Met Glu Glu Leu Gly     
#   140                                                                   
- Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Al - #a Met Pro Ala Phe Ala     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Le - #u Val Ala Ser His Leu     
#               175                                                       
- Gln                                                                     
- (2) INFORMATION FOR SEQ ID NO:305:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 177 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:305:                           
- Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Al - #a Ala Leu Gln Glu Lys     
#                15                                                       
- Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Gl - #u Glu Leu Val Leu Leu     
#            30                                                           
- Gly His Ser Leu Gly Ile Pro Trp Ala Pro Le - #u Ser Ser Cys Pro Ser     
#        45                                                               
- Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gl - #n Leu His Ser Gly Leu     
#    60                                                                   
- Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Gl - #u Gly Ile Ser Pro Glu     
#80                                                                       
- Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu As - #p Val Ala Asp Phe Ala     
#                95                                                       
- Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gl - #y Met Ala Pro Ala Leu     
#           110                                                           
- Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Al - #a Ser Ala Phe Gln Arg     
#       125                                                               
- Arg Ala Gly Gly Val Leu Val Ala Ser His Le - #u Gln Ser Phe Leu Glu     
#   140                                                                   
- Val Ser Tyr Arg Val Leu Arg His Leu Ala Gl - #n Pro Asp Met Ala Thr     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Se - #r Phe Leu Leu Lys Ser     
#               175                                                       
- Leu                                                                     
- (2) INFORMATION FOR SEQ ID NO:306:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 177 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:306:                           
- Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Ph - #e Leu Leu Lys Ser Leu     
#                15                                                       
- Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Al - #a Ala Leu Gln Glu Lys     
#            30                                                           
- Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Gl - #u Glu Leu Val Leu Leu     
#        45                                                               
- Gly His Ser Leu Gly Ile Pro Trp Ala Pro Le - #u Ser Ser Cys Pro Ser     
#    60                                                                   
- Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gl - #n Leu His Ser Gly Leu     
#80                                                                       
- Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Gl - #u Gly Ile Ser Pro Glu     
#                95                                                       
- Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu As - #p Val Ala Asp Phe Ala     
#           110                                                           
- Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gl - #y Met Ala Pro Ala Leu     
#       125                                                               
- Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Al - #a Ser Ala Phe Gln Arg     
#   140                                                                   
- Arg Ala Gly Gly Val Leu Val Ala Ser His Le - #u Gln Ser Phe Leu Glu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Val Ser Tyr Arg Val Leu Arg His Leu Ala Gl - #n Pro Asp Met Ala Thr     
#               175                                                       
- Pro                                                                     
- (2) INFORMATION FOR SEQ ID NO:307:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 177 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:307:                           
- Leu Leu Gly His Ser Leu Gly Ile Pro Trp Al - #a Pro Leu Ser Ser Cys     
#                15                                                       
- Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Le - #u Ser Gln Leu His Ser     
#            30                                                           
- Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Al - #a Leu Glu Gly Ile Ser     
#        45                                                               
- Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gl - #n Leu Asp Val Ala Asp     
#    60                                                                   
- Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Gl - #u Leu Gly Met Ala Pro     
#80                                                                       
- Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Al - #a Phe Ala Ser Ala Phe     
#                95                                                       
- Gln Arg Arg Ala Gly Gly Val Leu Val Ala Se - #r His Leu Gln Ser Phe     
#           110                                                           
- Leu Glu Val Ser Tyr Arg Val Leu Arg His Le - #u Ala Gln Pro Asp Met     
#       125                                                               
- Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pr - #o Gln Ser Phe Leu Leu     
#   140                                                                   
- Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gl - #y Asp Gly Ala Ala Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cy - #s His Pro Glu Glu Leu     
#               175                                                       
- Val                                                                     
- (2) INFORMATION FOR SEQ ID NO:308:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 177 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:308:                           
- Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gl - #n Leu Ala Gly Cys Leu     
#                15                                                       
- Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gl - #n Gly Leu Leu Gln Ala     
#            30                                                           
- Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Th - #r Leu Asp Thr Leu Gln     
#        45                                                               
- Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Tr - #p Gln Gln Met Glu Glu     
#    60                                                                   
- Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gl - #n Gly Ala Met Pro Ala     
#80                                                                       
- Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gl - #y Val Leu Val Ala Ser     
#                95                                                       
- His Leu Gln Ser Phe Leu Glu Val Ser Tyr Ar - #g Val Leu Arg His Leu     
#           110                                                           
- Ala Gln Pro Asp Met Ala Thr Pro Leu Gly Pr - #o Ala Ser Ser Leu Pro     
#       125                                                               
- Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Va - #l Arg Lys Ile Gln Gly     
#   140                                                                   
- Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Al - #a Thr Tyr Lys Leu Cys     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- His Pro Glu Glu Leu Val Leu Leu Gly His Se - #r Leu Gly Ile Pro Trp     
#               175                                                       
- Ala                                                                     
- (2) INFORMATION FOR SEQ ID NO:309:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 177 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:309:                           
- Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gl - #n Leu His Ser Gly Leu     
#                15                                                       
- Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Gl - #u Gly Ile Ser Pro Glu     
#            30                                                           
- Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu As - #p Val Ala Asp Phe Ala     
#        45                                                               
- Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gl - #y Met Ala Pro Ala Leu     
#    60                                                                   
- Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Al - #a Ser Ala Phe Gln Arg     
#80                                                                       
- Arg Ala Gly Gly Val Leu Val Ala Ser His Le - #u Gln Ser Phe Leu Glu     
#                95                                                       
- Val Ser Tyr Arg Val Leu Arg His Leu Ala Gl - #n Pro Asp Met Ala Thr     
#           110                                                           
- Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Se - #r Phe Leu Leu Lys Ser     
#       125                                                               
- Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gl - #y Ala Ala Leu Gln Glu     
#   140                                                                   
- Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pr - #o Glu Glu Leu Val Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pr - #o Leu Ser Ser Cys Pro     
#               175                                                       
- Ser                                                                     
- (2) INFORMATION FOR SEQ ID NO:310:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 177 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:310:                           
- Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu Hi - #s Ser Gly Leu Phe Leu     
#                15                                                       
- Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Il - #e Ser Pro Glu Leu Gly     
#            30                                                           
- Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Al - #a Asp Phe Ala Thr Thr     
#        45                                                               
- Ile Trp Gln Gln Met Glu Glu Leu Gly Met Al - #a Pro Ala Leu Gln Pro     
#    60                                                                   
- Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Al - #a Phe Gln Arg Arg Ala     
#80                                                                       
- Gly Gly Val Leu Val Ala Ser His Leu Gln Se - #r Phe Leu Glu Val Ser     
#                95                                                       
- Tyr Arg Val Leu Arg His Leu Ala Gln Pro As - #p Met Ala Thr Pro Leu     
#           110                                                           
- Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Le - #u Leu Lys Ser Leu Glu     
#       125                                                               
- Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Al - #a Leu Gln Glu Lys Leu     
#   140                                                                   
- Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Gl - #u Leu Val Leu Leu Gly     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- His Ser Leu Gly Ile Pro Trp Ala Pro Leu Se - #r Ser Cys Pro Ser Gln     
#               175                                                       
- Ala                                                                     
- (2) INFORMATION FOR SEQ ID NO:311:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 177 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:311:                           
- Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gl - #y Leu Phe Leu Tyr Gln     
#                15                                                       
- Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pr - #o Glu Leu Gly Pro Thr     
#            30                                                           
- Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Ph - #e Ala Thr Thr Ile Trp     
#        45                                                               
- Gln Gln Met Glu Glu Leu Gly Met Ala Pro Al - #a Leu Gln Pro Thr Gln     
#    60                                                                   
- Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gl - #n Arg Arg Ala Gly Gly     
#80                                                                       
- Val Leu Val Ala Ser His Leu Gln Ser Phe Le - #u Glu Val Ser Tyr Arg     
#                95                                                       
- Val Leu Arg His Leu Ala Gln Pro Asp Met Al - #a Thr Pro Leu Gly Pro     
#           110                                                           
- Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Ly - #s Ser Leu Glu Gln Val     
#       125                                                               
- Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gl - #n Glu Lys Leu Cys Ala     
#   140                                                                   
- Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Va - #l Leu Leu Gly His Ser     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cy - #s Pro Ser Gln Ala Leu     
#               175                                                       
- Gln                                                                     
- (2) INFORMATION FOR SEQ ID NO:312:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#acids    (A) LENGTH: 177 amino                                           
          (B) TYPE: amino acid                                            
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: peptide                                         
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:312:                           
- His Leu Ala Gln Pro Asp Met Ala Thr Pro Le - #u Gly Pro Ala Ser Ser     
#                15                                                       
- Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Gl - #u Gln Val Arg Lys Ile     
#            30                                                           
- Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Le - #u Cys Ala Thr Tyr Lys     
#        45                                                               
- Leu Cys His Pro Glu Glu Leu Val Leu Leu Gl - #y His Ser Leu Gly Ile     
#    60                                                                   
- Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gl - #n Ala Leu Gln Leu Ala     
#80                                                                       
- Gly Cys Leu Ser Gln Leu His Ser Gly Leu Ph - #e Leu Tyr Gln Gly Leu     
#                95                                                       
- Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Le - #u Gly Pro Thr Leu Asp     
#           110                                                           
- Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Th - #r Thr Ile Trp Gln Gln     
#       125                                                               
- Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gl - #n Pro Thr Gln Gly Ala     
#   140                                                                   
- Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Ar - #g Ala Gly Gly Val Leu     
145                 1 - #50                 1 - #55                 1 -   
#60                                                                       
- Val Ala Ser His Leu Gln Ser Phe Leu Glu Va - #l Ser Tyr Arg Val Leu     
#               175                                                       
- Arg                                                                     
- (2) INFORMATION FOR SEQ ID NO:313:                                      
-      (i) SEQUENCE CHARACTERISTICS:                                      
#pairs    (A) LENGTH: 531 base                                            
          (B) TYPE: nucleic acid                                          
          (C) STRANDEDNESS: unknown                                       
          (D) TOPOLOGY: unknown                                           
-     (ii) MOLECULE TYPE: other nucleic acid                              
#= "synthetic"DESCRIPTION: /desc                                          
-     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:313:                           
- CACCTTGCGC AGCCCGACAT GGCTACACCA TTAGGCCCTG CCAGCTCCCT GC - #CCCAGAGC   
  60                                                                      
- TTCCTGCTCA AGTCTTTAGA GCAAGTGAGG AAGATCCAGG GCGATGGCGC AG - #CGCTCCAG   
 120                                                                      
- GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GC - #TCGGACAC   
 180                                                                      
- TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GC - #AGCTGGCA   
 240                                                                      
- GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GC - #AGGCCCTG   
 300                                                                      
- GAAGGGATAT CCCCCGAGTT GGGTCCCACC TTGGACACAC TGCAGCTGGA CG - #TCGCCGAC   
 360                                                                      
- TTTGCCACCA CCATCTGGCA GCAGATGGAA GAACTGGGAA TGGCCCCTGC CC - #TGCAGCCC   
 420                                                                      
- ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AG - #GGGTCCTG   
 480                                                                      
#            531TGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG C                
__________________________________________________________________________

Claims (61)

What is claimed is:
1. A hematopoietic protein comprising; an amino acid sequence of the formula:
R1-L1-R2, R2-L1-R1, R1-R2, or R2-R1
wherein R1 is a biologically active human c-mpl ligand comprising a modified amino acid sequence selected from the group consisting of:
(a) an amino acid sequence of SEQ ID NO:256
wherein;
Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met;
Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn; and
wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus wherein new C-termini and N-termini are created between the amino acid reside pairs of SEQ ID NO:256 selected from the group consisting of:
26-27, 27-28, 28-29, 29-30, 30-31, 32-33, 33-34, 34-35, 36-37, 37-38, 38-39, 40-41, 41-42, 42-43, 43-44, 44-45, 46-47, 47-48, 48-49, 50-51, 51-52, 52-53, 53-54, 54-55, 55-56, 56-57, 57-58, 58-59, 59-60, 78-79, 79-80, 80-81, 81-82, 82-83, 83-84, 84-85, 85-86, 86-87, 87-88, 88-89, 108-109, 109-110, 110-111, 111-112, 112-113, 113-114, 114-115, 115-116, 116-117, 117-118, 118-119, 119-120, 120-121, 121-122, 122-123, 123-124, 124-125, 125-126, 126-127 or 127-128; and
(b) an amino acid sequence of SEQ ID NO:283
wherein;
Xaa at position 7 is Ser or Ala;
Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met;
Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn;
Xaa at position 151 is Ser or Ala;
wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus wherein new C-termini and N-termini are created between the amino acid reside pairs of SEQ ID NO:283 selected from the group consisting of:
2- 27. 27-28, 28-29, 29-30, 30-31, 32-33, 33-34, 34-35, 36-37, 37-38, 38-39, 40-41, 41-42, 42-43, 43-44, 44-45, 46-47, 47-48, 48-49, 50-51, 51-52, 52-53, 53-54, 54-55, 55-56, 56-57, 57-58, 58-59, 59-60, 78-79, 79-80, 80-81, 81-82, 82-83, 83-84, 84-85, 85-86, 86-87, 87-88, 88-89, 108-109, 109-110, 110-111, 111-112, 112-113, 113-114, 114-115, 115-116, 116-117, 117-118, 118-119, 119-120, 120-121, 121-122, 122-123, 123-124, 124-125, 125-126, 126-127 or 127-128;
R2 is selected from the group consisting of: a biologically active human IL-3 variant comprising a modified amino acid sequence of (SEQ ID NO:2)
wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
Xaa at position 36 is Asp, Leu, or Val;
Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
Xaa at position 38 is Asn, or Ala;
Xaa at position 40 is Leu, Trp, or Arg;
Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
Xaa at position 43 is Glu, Asn,. Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
Xaa at position 57 is Asn or Gly;
Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
Xaa at position 85 is Leu, Asn, Val, or Gln;
Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
Xaa at position 87 is Leu, Ser, Trp, or Gly;
Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln;
Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
Xaa at position 103 is Asp, or Ser;
Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp;
Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;
Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
Xaa at position 123 is Ala, Met, Glu, His, Ser., Pro, Tyr, or Leu;
wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; and wherein from 1 to 14 amino acids are optionally deleted from the N-terminus and/or from 1 to 15 amino acids are optionally deleted from the C-terminus of said modified human IL-3 amino acid sequence;
a colony stimulating factor, a cytokine, a lymphokine, an interleukin, and a hematopoietic growth factor;
L1 is a linker capable of linking R1 to R2; and
said hematopoietic protein is optionally immediately preceded by (methionine-1), (alanine-1) or (methionine-2, alanine-1).
2. The hematopoietic protein as recited in claim 1 wherein said protein is selected from the group consisting of;
SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, and SEQ ID NO:239.
3. A nucleic acid molecule encoding said hematopoietic protein of claim 2.
4. The nucleic acid molecule according to claim 3 selected from group consisting of:
SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, and SEQ ID NO:154.
5. The hematopoietic protein as recited in claim 1 wherein said c-mpl receptor agonist is selected from the group consisting of:
MetAlaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis              
LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuAlaValArg              
GluPheGlyGlyAsnMetAlaSerProAlaProProAlaAlaAspLeuArgValLeuSer              
LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis              
ProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThr              
GlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGly              
ValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeu              
SerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuPro              
ProGln (SEQ ID NO:284); and                                               
MetAlaGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeu              
LeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThr              
AlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysVal              
ArgPheLeuMetLeuValGlyGlySerThrLeuAlaValArgGluPheGlyGlyAsnMet              
AlaSerProAlaProProAlaAlaAspLeuArgValLeuSerLysLeuLeuArgAspSer              
HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVal              
LeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLys              
AlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGly              
GlnLeu (SEQ ID NO:285)
6. A nucleic acid molecule encoding said hematopoietic protein of claim 5.
7. A nucleic acid molecule encoding said hematopoietic protein of claim 1.
8. A method for selective ex vivo expansion of hematopoietic stem cells, comprising the steps of;
(a) separating hematopoietic stem cells from other cells;
(b) culturing the separated hematopoietic stem cells from step (a) with a selected culture medium comprising; an amount of the hematopoietic protein of claim 1, effective to expand said hematopoietic stem cells; and
(c) harvesting the cultured hematopoietic cells of step (b).
9. A method for treatment of a patient having a hematopoietic disorder, comprising the steps of;
(a) removing hematopoietic cells from said patient;
(b) separating hematopoietic stem cells from other cells removed from said patient;
(c) culturing said separated hematopoietic stem cells from step (b) with a selected culture medium comprising; an amount of the hematopoietic protein of claim 1 effective to expand and/or differentiate the hematopoietic stem cells;
(d) harvesting the cultured hematopoietic cells from step (c); and
(e) introducing the cultured hematopoietic cells from step (d) into said patient to increase the number of hematopoietic cells.
10. A method of expanding the transducing hematopoietic cells for use in gene therapy, comprising the steps of;
(a) removing hematopoietic cells from a patient;
(b) separating hematopoietic stem cells from other cells removed from the patient in step (a);
(c) culturing said separated hematopoietic stem cells from step (b) with a selected culture medium comprising; an amount of the hematopoietic protein of claim 1 effective to expand the hematopoietic stem cells;
(d) transducing the cultured hematopoietic cells from step (c) by introducing DNA into said cultured hematopoietic cells; and
(e) harvesting said transduced hematopoietic cells.
11. A pharmaceutical composition comprising; the hematopoietic protein according to claim 1; at least one colony stimulating factor, cytokine, lymphokine, interleukin, or hematopoietic growth factor selected from the group consisting of: GM-CSF, G-CSF, c-mpl ligand (TPO), MGDF, M-CSF, erythropoietin (EPO), IL-1, IL-4, IL-2, IL-3, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-15, IL-16, LIF, flt3 ligand, and stem cell factor (SCF); and a pharmaceutically acceptable carrier.
12. A method of stimulating the production of hematopoietic cells in a patient comprising the step of; administering to said patient an amount of the composition as recited in claim 11, effective to stimulate the production of hematopoietic cells.
13. A method for selective ex vivo expansion of hematopoietic cells, comprising the steps of;
(a) culturing hematopoietic cells with a culture medium comprising; an amount of the composition of claim 11, effective to expand said hematopoietic cells; and
(b) harvesting the cultured hematopoietic cells of step (a).
14. A method for selective ex vivo expansion of hematopoietic stem cells, comprising the steps of;
(a) separating hematopoietic stem cells from other cells;
(b) culturing the separated hematopoietic stem cells from step (a) with a selected culture medium comprising; an amount of the composition of claim 11, effective to expand said hematopoietic stem cells; and
(c) harvesting the cultured hematopoietic cells of step (b).
15. A method for treatment of a patient having a hematopoietic disorder, comprising the steps of;
(a) removing hematopoietic cells from said patient;
(b) separating hematopoietic stem cells from other cells removed from said patient;
(c) culturing said separated hematopoietic stem cells from step (b) with a selected culture medium comprising; an amount of the composition of claim 11, effective to expand and/or differentiate the hematopoietic stem cells;
(d) harvesting the cultured hematopoietic cells from step (c); and
(e) introducing the cultured hematopoietic cells from step (d) into said patient to increase the number of hematopoietic cells.
16. A method of expanding and transducing hematopoietic cells for use in gene therapy, comprising the steps of;
(a) removing hematopoietic cells from a patient;
(b) separating hematopoietic stem cells from other cells removed from the patient in step (a);
(c) culturing said separated hematopoietic stem cells from step (b) with a selected culture medium comprising; an amount of the hematopoietic protein of claim 11 effective to expand the hematopoietic stem cells;
(d) transducing the cultured hematopoietic cells from step (c) by introducing DNA into said cultured hematopoietic cells; and
(e) harvesting said transduced hematopoietic cells.
17. A hematopoietic protein comprising; an amino acid sequence of the formula:
R1-L1-R2, R2-L1-R1, R1-R2, or R2-R1
wherein R1 is a biologically active human c-mpl ligand comprising a modified amino acid sequence of SEQ ID NO:256
wherein;
Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met;
Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn; and
wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus wherein new C-termini and N-termini are created between the amino acid reside pairs of SEQ ID NO:256 selected from the group consisting of:
26-27, 27-28, 28-29, 29-30, 30-31, 32-33, 33-34, 34-35, 36-37, 37-38, 38-39, 40-41, 41-42, 42-43, 43-44, 44-45, 46-47, 47-48, 48-49, 50-51, 51-52, 52-53, 53-54, 54-55, 55-56, 56-57, 57-58, 58-59, 59-60, 78-79, 79-80, 80-81, 81-82, 82-83, 83-84, 84-85, 85-86, 86-87, 87-88, 88-89, 108-109, 109-110, 110-111, 111-112, 112-113, 113-114, 114-115, 115-116, 116-117, 117-118, 118-119, 119-120, 120-121, 121-122, 122-123, 123-124, 124-125, 125-126, 126-127 or 127-128;
R2 is selected from the group consisting of: a biologically active human IL-3 variant comprising a modified amino acid sequence of SEQ ID NO:2
wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
Xaa at position 36 is Asp, Leu, or Val;
Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
Xaa at position 38 is Asn, or Ala;
Xaa at position 40 is Leu, Trp, or Arg;
Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
Xaa at position 57 is Asn or. Gly;
Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
Xaa at position 85 is Leu, Asn, Val, or Gln;
Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
Xaa at position 87 is Leu, Ser, Trp, or Gly;
Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln;
Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
Xaa at position 103 is Asp, or Ser;
Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp;
Xaa at position Ill is Leu, Ile, Arg, Asp, or Met;
Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser,.Asn, His, Ala, Tyr, Phe, Gln, or Ile;
Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
wherein from 1 to 14 amino acids are optionally deleted from the N-terminus and/or from 1 to 15 amino acids are optionally deleted from the C-terminus of said modified human IL-3 amino acid sequence; and wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3;
a colony stimulating factor, a cytokine, a lymphokine, an interleukin, and a hematopoietic growth factor;
L1 is a linker capable of linking R1 to R2; and
said hematopoietic protein is optionally immediately preceded by (methionine-1), (alanine-1) or (methionine-2, alanine-1).
18. A nucleic acid molecule encoding said hematopoietic protein of claim 17.
19. The hematopoietic protein of claim 1 or 17 wherein said colony stimulating factor, cytokine, interleukin, or hematopoietic growth factor, is selected from the group consisting of GM-CSF, G-CSF, G-CSF Ser17, c-mpl ligand (TPO), MGDF, M-CSF, erythropoietin (EPO), IL-1, IL-4, IL-2, IL-3, IL-5, IL 6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-15, LIF, flt3 ligand, human growth hormone, and stem cell factor (SCF).
20. The hematopoietic protein as recited in claim 19 wherein said linker (L2) is selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 247 and SEQ ID NO: 248.
21. A method for treatment of a patient having a hematopoietic disorder, comprising the steps of;
(a) removing hematopoietic cells from said patient;
(b) separating hematopoietic stem cells from other cells removed from said patient;
(c) culturing said separated hematopoietic stem cells from step (b) with a selected culture medium comprising; an amount of the hematopoietic protein of claim 20 effective to expand and/or differentiate the hematopoietic stem cells;
(d) harvesting the cultured hematopoietic cells from step (c); and
(e) introducing the cultured hematopoietic cells from step (d) into said patient to increase the number of hematopoietic cells.
22. A nucleic acid molecule encoding said hematopoietic protein of claim 20.
23. A method of producing a hematopoietic protein comprising: growing under suitable nutrient conditions, a host cell transformed or transfected with a replicable vector comprising a nucleic acid molecule of claim 22 under conditions which result in the expression of said hematopoietic protein and recovering said hematopoietic protein.
24. A pharmaceutical composition comprising; the hematopoietic protein according to claim 20 and a pharmaceutically acceptable carrier.
25. A method of stimulating the production of hematopoietic cells in a patient comprising the step of; administering to said patient an amount of the hematopoietic protein as recited in claim 20, effective to stimulate the production of hematopoietic cells.
26. A method for selective ex vivo expansion of hematopoietic stem cells, comprising the steps of;
(a) separating hematopoietic stem cells from other cells;
(b) culturing the separated hematopoietic stem cells from step (a) with a selected culture medium comprising; an amount of the hematopoietic protein of claim 20, effective to expand said hematopoietic stem cells; and
(c) harvesting the cultured hematopoietic cells of step (b).
27. A method of expanding and transducing hematopoietic cells for use in gene therapy, comprising the steps of;
(a) removing hematopoietic cells from a patient;
(b) separating hematopoietic stem cells from other cells removed from the patient in step (a);
(c) culturing said separated hematopoietic stem cells from step (b) with a selected culture medium comprising; an amount of the hematopoietic protein of claim 20 effective to expand the hematopoietic stem cells;
(d) transducing the cultured hematopoietic cells from step (c) by introducing DNA into said cultured hematopoietic cells; and
(e) harvesting said transduced hematopoietic cells.
28. A nucleic acid molecule encoding said hematopoietic protein of claim 19.
29. A method of producing a hematopoietic protein comprising: growing under suitable nutrient conditions, a host cell transformed or transfected with a replicable vector comprising a nucleic acid molecule of claim 28 under conditions which result in the expression of said hematopoietic protein and recovering said hematopoietic protein.
30. A pharmaceutical composition comprising; the hematopoietic protein according to claim 19 and a pharmaceutically acceptable carrier.
31. A method of stimulating the production of hematopoietic cells in a patient comprising the step of; administering to said patient an amount of the hematopoietic protein as recited in claim 19, effective to stimulate the production of hematopoietic cells.
32. A method for selective ex vivo expansion of hematopoietic cells, comprising the steps of;
(a) culturing hematopoietic cells with a culture medium comprising; an amount of the hematopoietic protein of claim 19, effective to expand said hematopoietic cells; and
(b) harvesting the cultured hematopoietic cells of step (a).
33. A method for selective ex vivo expansion of hematopoietic stem cells, comprising the steps of;
(a) separating hematopoietic stem cells from other cells;
(b) culturing the separated hematopoietic stem cells from step (a) with a selected culture medium comprising; an amount of the hematopoietic protein of claim 19, effective to expand said hematopoietic stem cells; and
(c) harvesting the cultured hematopoietic cells of step (b).
34. A method for treatment of a patient having a hematopoietic disorder, comprising the steps of;
(a) removing hematopoietic cells from said patient;
(b) separating hematopoietic stem cells from other cells removed from said patient;
(c) culturing said separated hematopoietic stem cells from step (b) with a selected culture medium comprising; an amount of the hematopoietic protein of claim 19 effective to expand and/or differentiate the hematopoietic stem cells;
(d) harvesting the cultured hematopoietic cells from step (c); and
(e) introducing the cultured hematopoietic cells from step (d) into said patient to increase the number of hematopoietic cells.
35. A method of expanding and transducing hematopoietic cells for use in gene therapy, comprising the steps of;
(a) removing hematopoietic cells from a patient;
(b) separating hematopoietic stem cells from other cells removed from the patient in step (a);
(c) culturing said separated hematopoietic stem cells from step (b) with a selected culture medium comprising; an amount of the hematopoietic protein of claim 19 effective to expand the hematopoietic stem cells;
(d) transducing the cultured hematopoietic cells from step (c) by introducing DNA into said cultured hematopoietic cells; and
(e) harvesting said transduced hematopoietic cells.
36. A hematopoietic protein comprising; an amino acid sequence of the formula:
R1-L1-R2, R2-L1-R1, R1-R2, or R2-R1
wherein R1 is a biologically active human c-mpl ligand comprising a modified amino acid sequence of SEQ ID NO:256
wherein;
Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met;
Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn; and
wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus wherein new C-termini and N-termini are created between the amino acid reside pairs of SEQ ID NO:256 selected from the group consisting of:
2- 27. 27-28, 28-29, 29-30, 30-31, 32-33, 33-34, 34-35, 36-37, 37-38, 38-39, 40-41, 41-42, 42-43, 43-44, 44-45, 46-47, 47-48, 48-49, 50-51, 51-52, 52-53, 53-54, 54-55, 55-56, 56-57, 57-58, 58-59, 59-60, 78-79, 79-80, 80-81, 81-82, 82-83, 83-84, 84-85, 85-86, 86-87, 87-88, 88-89, 108-109, 109-110, 110-111, 111-112, 112-113, 113-114, 114-115, 115-116, 116-117, 117-118, 118-119, 119-120, 120-121, 121-122, 122-123, 123-124, 124-125, 125-126, 126-127 or 127-128;
R2 is a biologically active human IL-3 variant comprising a modified amino acid sequence of SEQ ID NO:2
wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
Xaa at position 36 is Asp, Leu, or Val;
Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
Xaa at position 38 is Asn, or Ala;
Xaa at position 40 is Leu, Trp, or Arg;
Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
Xaa at position 57 is Asn or Gly;
Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
Xaa at position 85 is Leu, Asn, Val, or Gln;
Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
Xaa at position 87 is Leu, Ser, Trp, or Gly;
Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln;
Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
Xaa at position 103 is Asp, or Ser;
Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp;
Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;
Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; and wherein from 1 to 14 amino acids are optionally deleted from the N-terminus and/or from 1 to 15 amino acids are optionally deleted from the C-terminus of said modified human IL-3 amino acid sequence;
L1 is a linker capable of linking R1 to R2; and
said hematopoietic protein is optionally immediately preceded by (methionine-1), (alanine-1) or (methionine-2, alanine-1).
37. The hematopoietic protein as recited in claim 36 wherein in said modified human IL-3 sequence the amino acids which differ from the corresponding residue in native human interleukin-3 are selected from the group consisting of:
position 42 wherein Xaa is Gly, Asp, Ser, Ile, Leu, Met, Tyr, or Ala;
position 45 wherein Xaa is Gln, Val, Met or Asn;
position 46 wherein Xaa is Asp, Ser, Gln, His or Val;
position 50 wherein Xaa is Glu or Asp;
position 51 wherein Xaa is Asn, Pro or Thr;
position 62 wherein Xaa is Asn or Pro;
position 76 wherein Xaa is Ser, or Pro;
position 82 wherein Xaa is Leu, Trp, Asp, Asn Glu, His, Phe, Ser or Tyr;
position 95 wherein Xaa is His, Arg, Thr, Asn or Ser;
position 98 wherein Xaa is His, Ile, Leu, Ala, Gln, Lys, Met, Ser, Tyr or Val;
position 100 wherein Xaa is Lys or Arg;
position 101 wherein Xaa is Asp;
position 105 wherein Xaa is Asn, or Pro;
position 108 wherein Xaa is Arg, Ala, or Ser;
position 116 wherein Xaa is Lys;
position 121 wherein Xaa is Ala, or Ile;
position 122 wherein Xaa is Gln, or Ile;
position 123 wherein Xaa is Ala, Met or Glu.
38. A nucleic acid molecule encoding said hematopoietic protein of claim 37.
39. The hematopoietic protein as recited in claim 36 wherein said modified human IL-3 sequence is selected from the group consisting of SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, and SEQ ID NO: 228.
40. A nucleic acid molecule encoding said hematopoietic protein of claim 39.
41. The hematopoietic protein as recited in claim 36 wherein said modified human IL-3 sequence differs from native human IL-3 by substitution of Asp for Glu at position 50.
42. A nucleic acid molecule encoding said hematopoietic protein of claim 41.
43. A nucleic acid molecule encoding said hematopoietic protein of claim 36.
44. A hematopoietic protein comprising an amino acid sequence of the formula:
R1-L1-R2, R2-L1-R1, R1-R2, or R2-R1
wherein R1 is a biologically active human c-mpl ligand comprising a modified amino acid sequence of SEQ ID NO:256
wherein;
Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met;
Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn; and
wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus wherein new C-termini and N-termini are created between the amino acid reside pairs of SEQ ID NO:256 selected from the group consisting of:
2- 27. 27-28, 28-29, 29-30, 30-31, 32-33, 33-34, 34-35, 36-37, 37-38, 38-39, 40-41, 41-42, 42-43, 43-44, 44-45, 46-47, 47-48, 48-49, 50-51, 51-52, 52-53, 53-54, 54-55, 55-56, 56-57, 57-58, 58-59, 59-60, 78-79, 79-80, 80-81, 81-82, 82-83, 83-84, 84-85, 85-86, 86-87, 87-88, 88-89, 108-109, 109-110, 110-111, 111-112, 112-113, 113-114, 114-115, 115-116, 116-117, 117-118, 118-119, 119-120, 120-121, 121-122, 122-123, 123-124, 124-125, 125-126, 126-127 or 127-128;
wherein R2 is G-CSF or G-CSF Ser17;
L1 is a linker capable of linking R1 to R2; and
said hematopoietic protein is optionally immediately preceded by (methionine-1), (alanine-1) or (methionine-2, alanine-1).
45. A nucleic acid molecule encoding said hematopoietic protein of claim 44.
46. The hematopoietic protein as recited in claim 1, 17, 36, 37, 39, 41, or 44 wherein said linker (L2) is selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 247 and SEQ ID NO: 248.
47. A nucleic acid molecule encoding said hematopoietic protein of claim 46.
48. A method of producing a hematopoietic protein comprising: growing under suitable nutrient conditions, a host cell transformed or transfected with a replicable vector comprising a nucleic acid molecule of claim 47 under conditions which result in the expression of said hematopoietic protein and recovering said hematopoietic protein.
49. A pharmaceutical composition comprising; the hematopoietic protein according to claim 46 and a pharmaceutically acceptable carrier.
50. A method of stimulating the production of hematopoietic cells in a patient comprising the step of; administering to said patient an amount of the hematopoietic protein as recited in claim 46, effective to stimulate the production of hematopoietic cells.
51. A method for selective ex vivo expansion of hematopoietic cells, comprising the steps of;
(a) culturing hematopoietic cells with a culture medium comprising; an amount of the hematopoietic protein of claim 46, effective to expand said hematopoietic cells; and
(b) harvesting the cultured hematopoietic cells of step (a).
52. A method for selective ex vivo expansion of hematopoietic stem cells, comprising the steps of;
(a) separating hematopoietic stem cells from other cells;
(b) culturing the separated hematopoietic stem cells from step (a) with a selected culture, medium comprising; an amount of the hematopoietic protein of claim 46, effective to expand said hematopoietic stem cells; and
(c) harvesting the cultured hematopoietic cells of step (b).
53. A method for treatment of a patient having a hematopoietic disorder, comprising the steps of;
(a) removing hematopoietic cells from said patient;
(b) separating hematopoietic stem cells from other cells removed from said patient;
(c) culturing said separated hematopoietic stem cells from step (b) with a selected culture medium comprising; an amount of the hematopoietic protein of claim 46 effective to expand and/or differentiate the hematopoietic stem cells;
(d) harvesting the cultured hematopoietic cells from step (c); and
(e) introducing the cultured hematopoietic cells from step (d) into said patient to increase the number of hematopoietic cells.
54. A method of expanding and transducing hematopoietic cells for use in gene therapy, comprising the steps of;
(a) removing hematopoietic cells from a patient;
(b) separating hematopoietic stem cells from other cells removed from the patient in step (a);
(c) culturing said separated hematopoietic stem cells from step (b) with a selected culture medium comprising; an amount of the hematopoietic protein of claim 46 effective to expand the hematopoietic stem cells;
(d) transducing the cultured hematopoietic cells from step (c) by introducing DNA into said cultured hematopoietic cells; and
(e) harvesting said transduced hematopoietic cells.
55. A method of producing a hematopoietic protein comprising: growing under suitable nutrient conditions, a host cell transformed or transfected with a replicable vector comprising a nucleic acid molecule of claim 7, 18, 43, 38, 40, 42, 45, 3, 4, or 6 under conditions which result in the expression of said hematopoietic protein and recovering said hematopoietic protein.
56. A pharmaceutical composition comprising; the hematopoietic protein according to claim 1, 17, 36, 37, 39, 41, 44, 2, or 5 and a pharmaceutically acceptable carrier.
57. A method of stimulating the production of hematopoietic cells in a patient comprising the step of; administering to said patient an amount of the hematopoietic protein as recited in claim 1, 17, 36, 37, 39, 41, 44, 2, or 5, effective to stimulate the production of hematopoietic cells.
58. A method for selective ex vivo expansion of hematopoietic cells, comprising the steps of;
(a) culturing hematopoietic cells with a culture medium comprising; an amount of the hematopoietic protein of claim 1, 17, 36, 37, 39, 41, 44, 2, or 5, effective to expand said hematopoietic cells; and
(b) harvesting the cultured hematopoietic cells of step (a).
US08/835,162 1995-10-05 1997-04-04 Multi-functional hematopoietic fusion proteins between sequence rearranged C-MPL receptor agonists and other hematopoietic factors Expired - Fee Related US6066318A (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US08/835,162 US6066318A (en) 1995-10-05 1997-04-04 Multi-functional hematopoietic fusion proteins between sequence rearranged C-MPL receptor agonists and other hematopoietic factors
US09/510,238 US6730303B1 (en) 1995-10-05 2000-02-22 Fused G-CSF and IL-3 proteins and uses thereof
US10/695,584 US20040171115A1 (en) 1995-10-05 2003-10-27 Multi-functional hematopoietic fusion proteins between sequence rearranged G-CSF receptor agonists and other hematopoietic factors

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US483495P 1995-10-05 1995-10-05
PCT/US1996/015774 WO1997012985A2 (en) 1995-10-05 1996-10-04 Multi-functional hematopoietic receptor agonists
US08/835,162 US6066318A (en) 1995-10-05 1997-04-04 Multi-functional hematopoietic fusion proteins between sequence rearranged C-MPL receptor agonists and other hematopoietic factors

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
PCT/US1996/015774 Continuation-In-Part WO1997012985A2 (en) 1995-10-05 1996-10-04 Multi-functional hematopoietic receptor agonists
US08836659 Continuation-In-Part 1997-05-16

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US09/510,238 Division US6730303B1 (en) 1995-10-05 2000-02-22 Fused G-CSF and IL-3 proteins and uses thereof

Publications (1)

Publication Number Publication Date
US6066318A true US6066318A (en) 2000-05-23

Family

ID=32179236

Family Applications (3)

Application Number Title Priority Date Filing Date
US08/835,162 Expired - Fee Related US6066318A (en) 1995-10-05 1997-04-04 Multi-functional hematopoietic fusion proteins between sequence rearranged C-MPL receptor agonists and other hematopoietic factors
US09/510,238 Expired - Fee Related US6730303B1 (en) 1995-10-05 2000-02-22 Fused G-CSF and IL-3 proteins and uses thereof
US10/695,584 Abandoned US20040171115A1 (en) 1995-10-05 2003-10-27 Multi-functional hematopoietic fusion proteins between sequence rearranged G-CSF receptor agonists and other hematopoietic factors

Family Applications After (2)

Application Number Title Priority Date Filing Date
US09/510,238 Expired - Fee Related US6730303B1 (en) 1995-10-05 2000-02-22 Fused G-CSF and IL-3 proteins and uses thereof
US10/695,584 Abandoned US20040171115A1 (en) 1995-10-05 2003-10-27 Multi-functional hematopoietic fusion proteins between sequence rearranged G-CSF receptor agonists and other hematopoietic factors

Country Status (1)

Country Link
US (3) US6066318A (en)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6261550B1 (en) 1993-01-28 2001-07-17 Amgen Inc. G-CSF hybrid molecules and pharmaceutical compositions
US20040028661A1 (en) * 2002-08-07 2004-02-12 Bartelmez Stephen H. Expansion of cells using thrombopoietin and anti-transforming growth factor-beta
US20050095684A1 (en) * 2000-01-10 2005-05-05 Maxygen Holdings Ltd. G-CSF conjugates
US20060084793A1 (en) * 2000-01-10 2006-04-20 Maxygen Holdings, Ltd. G-CSF polypeptides and conjugates
US20060286069A1 (en) * 2000-01-10 2006-12-21 Maxygen Holdings, Ltd. G-CSF Conjugates
US20070196911A1 (en) * 2004-07-12 2007-08-23 Giovanni Mambrini Devices and methods for growing human cells
US7381805B2 (en) 2005-06-01 2008-06-03 Maxygen Holdings, Ltd. Compositions comprising mixtures of positional PEG isomers of PEGylated G-CSF
US9181531B2 (en) 2011-12-21 2015-11-10 Apse, Llc Process for purifying VLPs
EP3222274A1 (en) 2013-06-19 2017-09-27 Apse Llc Compositions and methods using capsids resistant to hydrolases

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008513356A (en) * 2004-08-09 2008-05-01 アリオス バイオファーマ インク． Synthetic advanced glycosylated protease resistant polypeptide variants, oral formulations and methods using the same
US7597884B2 (en) * 2004-08-09 2009-10-06 Alios Biopharma, Inc. Hyperglycosylated polypeptide variants and methods of use
KR100735784B1 (en) * 2005-07-20 2007-07-06 재단법인 목암생명공학연구소 Mutant of granulocyte-colony stimulating factorG-CSF and chemically conjugated polypeptide thereof
EP2694550B1 (en) * 2011-04-01 2019-11-27 Universität Stuttgart Recombinant tnf ligand family member polypeptides with antibody binding domain and uses thereof
LT6161B (en) 2013-09-27 2015-06-25 Uab Profarma Fused proteins of granulocyte colony-stimulating factor with other partners of growh factor, preferably with stem cell factor, and method of preparation thereof

Citations (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0225579A2 (en) * 1985-12-02 1987-06-16 G.D. Searle & Co. Covalently linked polypeptide cell modulators
US4810643A (en) * 1985-08-23 1989-03-07 Kirin- Amgen Inc. Production of pluripotent granulocyte colony-stimulating factor
US4877729A (en) * 1986-07-14 1989-10-31 Genetics Institute, Inc. Recombinant DNA encoding novel family of primate hematopoietic growth factors
US4959455A (en) * 1986-07-14 1990-09-25 Genetics Institute, Inc. Primate hematopoietic growth factors IL-3 and pharmaceutical compositions
WO1990012877A1 (en) * 1989-04-19 1990-11-01 Cetus Corporation Multifunctional m-csf proteins and genes encoding therefor
US4999291A (en) * 1985-08-23 1991-03-12 Amgen Inc. Production of human pluripotent granulocyte colony-stimulating factor
WO1992004455A1 (en) * 1990-08-29 1992-03-19 Genetics Institute, Inc. Multidomain hematopoiesis stimulators
WO1992006116A1 (en) * 1990-09-28 1992-04-16 Ortho Pharmaceutical Corporation Hybrid growth factors
US5399345A (en) * 1990-05-08 1995-03-21 Boehringer Mannheim, Gmbh Muteins of the granulocyte colony stimulating factor
WO1995018858A1 (en) * 1994-01-03 1995-07-13 Genentech, Inc. Thrombopoietin
WO1995021254A1 (en) * 1994-02-04 1995-08-10 G. D. Searle & Co. Multivariant il-3 hematopoiesis fusion protein
WO1995021197A1 (en) * 1994-02-04 1995-08-10 G.D. Searle & Co. Il-3 variant hematopoiesis fusion protein
EP0675201A1 (en) * 1994-03-31 1995-10-04 Amgen Inc. Compositions and methods for stimulating megakaryocyte growth and differentiation
WO1995027732A2 (en) * 1994-04-08 1995-10-19 The Government Of The United States Of America, Represented By The Secretary Of The Department Of Health And Human Services Circularly permuted ligands and circularly permuted chimeric molecules
EP0783003A1 (en) * 1995-04-26 1997-07-09 Kyowa Hakko Kogyo Co., Ltd. Novel polypeptides
US5677149A (en) * 1992-11-24 1997-10-14 G.D. Searle & Co., Interleukin-3 (IL-3) mutant polypeptides and their recombinant production
US5756083A (en) * 1995-02-15 1998-05-26 Amgen Inc. Mpl ligand analogs

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3672359B2 (en) * 1995-07-24 2005-07-20 生化学工業株式会社 Heparan sulfate 2-O-sulfotransferase
US6100070A (en) * 1995-10-05 2000-08-08 G. D. Searle & Co. G-CSF receptor agonists

Patent Citations (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4810643A (en) * 1985-08-23 1989-03-07 Kirin- Amgen Inc. Production of pluripotent granulocyte colony-stimulating factor
US4999291A (en) * 1985-08-23 1991-03-12 Amgen Inc. Production of human pluripotent granulocyte colony-stimulating factor
EP0225579A2 (en) * 1985-12-02 1987-06-16 G.D. Searle & Co. Covalently linked polypeptide cell modulators
US4877729A (en) * 1986-07-14 1989-10-31 Genetics Institute, Inc. Recombinant DNA encoding novel family of primate hematopoietic growth factors
US4959455A (en) * 1986-07-14 1990-09-25 Genetics Institute, Inc. Primate hematopoietic growth factors IL-3 and pharmaceutical compositions
WO1990012877A1 (en) * 1989-04-19 1990-11-01 Cetus Corporation Multifunctional m-csf proteins and genes encoding therefor
US5567611A (en) * 1989-04-19 1996-10-22 Cetus Onocology Corporation Multifunctional M-CSF proteins and genes encoding therefor
US5399345A (en) * 1990-05-08 1995-03-21 Boehringer Mannheim, Gmbh Muteins of the granulocyte colony stimulating factor
WO1992004455A1 (en) * 1990-08-29 1992-03-19 Genetics Institute, Inc. Multidomain hematopoiesis stimulators
WO1992006116A1 (en) * 1990-09-28 1992-04-16 Ortho Pharmaceutical Corporation Hybrid growth factors
US5817486A (en) * 1992-11-24 1998-10-06 G. D. Searle & Co. Recombinant human interleukin-3 (IL-3) multiple mutation polypeptides
US5738849A (en) * 1992-11-24 1998-04-14 G. D. Searle & Co. Interleukin-3 (IL-3) variant fusion proteins, their recombinant production, and therapeutic compositions comprising them
US5677149A (en) * 1992-11-24 1997-10-14 G.D. Searle & Co., Interleukin-3 (IL-3) mutant polypeptides and their recombinant production
WO1995018858A1 (en) * 1994-01-03 1995-07-13 Genentech, Inc. Thrombopoietin
WO1995021254A1 (en) * 1994-02-04 1995-08-10 G. D. Searle & Co. Multivariant il-3 hematopoiesis fusion protein
WO1995021197A1 (en) * 1994-02-04 1995-08-10 G.D. Searle & Co. Il-3 variant hematopoiesis fusion protein
EP0675201A1 (en) * 1994-03-31 1995-10-04 Amgen Inc. Compositions and methods for stimulating megakaryocyte growth and differentiation
US5635599A (en) * 1994-04-08 1997-06-03 The United States Of America As Represented By The Department Of Health And Human Services Fusion proteins comprising circularly permuted ligands
WO1995027732A2 (en) * 1994-04-08 1995-10-19 The Government Of The United States Of America, Represented By The Secretary Of The Department Of Health And Human Services Circularly permuted ligands and circularly permuted chimeric molecules
US5756083A (en) * 1995-02-15 1998-05-26 Amgen Inc. Mpl ligand analogs
EP0783003A1 (en) * 1995-04-26 1997-07-09 Kyowa Hakko Kogyo Co., Ltd. Novel polypeptides

Non-Patent Citations (51)

* Cited by examiner, † Cited by third party
Title
Buchwalder et al, "A fully active variant of Dihydrofolate Reductase with a circularly permuted sequence", Biochemistry, 1992, vol. 31, pp. 1621-1630.
Buchwalder et al, A fully active variant of Dihydrofolate Reductase with a circularly permuted sequence , Biochemistry, 1992, vol. 31, pp. 1621 1630. *
Cunningham et al, "Favion versus concanavalin A: Circularly permuted amino acid sequences", Proc. Natl. Acad. Sci. USA, Jul. 1979, vol. 76, No. 7, pp. 3218-3222.
Cunningham et al, Favion versus concanavalin A: Circularly permuted amino acid sequences , Proc. Natl. Acad. Sci. USA, Jul. 1979, vol. 76, No. 7, pp. 3218 3222. *
D.L. Eaton et al., Blood 84(10) Suppl. Abstract 948, 1994. *
Garrett et al, "Are turns required for the folding of ribonuclease T1?", Protein Science, 1996, vol. 5., pp. 204-211.
Garrett et al, Are turns required for the folding of ribonuclease T1 , Protein Science, 1996, vol. 5., pp. 204 211. *
Goldenberg et al, "Circular and Circularly Permuted Forms of Bovine Pancreatic Trypsin Inhibitor", J. Mol. Biol. 1983, vol. 165, pp. 407-413.
Goldenberg et al, Circular and Circularly Permuted Forms of Bovine Pancreatic Trypsin Inhibitor , J. Mol. Biol. 1983, vol. 165, pp. 407 413. *
Hahn et al, "Native-like in vivo folding of a circularly permuted jellyroll protein shown by crystal structure analysis", Proc. Natl. Acad. Sci. USA, 1994, vol. 91, pp. 10417-10421.
Hahn et al, Native like in vivo folding of a circularly permuted jellyroll protein shown by crystal structure analysis , Proc. Natl. Acad. Sci. USA, 1994, vol. 91, pp. 10417 10421. *
Hemperly et al, "Circular permutation of amino acid sequences among legume lectins", TIBS, 1983, pp. 100-102.
Hemperly et al, Circular permutation of amino acid sequences among legume lectins , TIBS, 1983, pp. 100 102. *
Horlick et al, "Permuteins of interleukin 1B--a simplified approach for the construction of permutated proteins having new termini", Protein Engineering, USA, 1992, vol. 5, pp. 427-431.
Horlick et al, Permuteins of interleukin 1B a simplified approach for the construction of permutated proteins having new termini , Protein Engineering, USA, 1992, vol. 5, pp. 427 431. *
Koebnik et al, "Membrane Assembly of Circulary Permuted Variants", JMB, 1995, vol. 250, pp. 617-626.
Koebnik et al, Membrane Assembly of Circulary Permuted Variants , JMB, 1995, vol. 250, pp. 617 626. *
Komar et al, "Kinetics of translation" FEBS Letters, 1995 vol. 376, pp. 195-198.
Komar et al, Kinetics of translation FEBS Letters, 1995 vol. 376, pp. 195 198. *
Kreitman et al, "A circularly permuted recombinant interleukin 4 toxin with increase activity", Proc. Natl. Acad. Sci. USA, 1993, vol. 91, pp. 6889-3893.
Kreitman et al, "Circularly permuted interleukin 4 retains proliferative and binding activity", Cytokine, 1995, vol. 7, No. 4, pp. 311-318.
Kreitman et al, A circularly permuted recombinant interleukin 4 toxin with increase activity , Proc. Natl. Acad. Sci. USA, 1993, vol. 91, pp. 6889 3893. *
Kreitman et al, Circularly permuted interleukin 4 retains proliferative and binding activity , Cytokine, 1995, vol. 7, No. 4, pp. 311 318. *
Li et al, "Degradation of Ornithine Decarboxylase", Mol. and Cel. Biol. 1993, vol. 13, No. 4, pp. 2377-2383.
Li et al, Degradation of Ornithine Decarboxylase , Mol. and Cel. Biol. 1993, vol. 13, No. 4, pp. 2377 2383. *
Lin et al, "Rearranging the domains of pepsinogen", Protein Science, 1995, vol. 4, pp. 159-166.
Lin et al, Rearranging the domains of pepsinogen , Protein Science, 1995, vol. 4, pp. 159 166. *
Luger et al, "An 8-fold Ba Barrel Protein with Redundant Folding Possibilities", Protein Engineering, vol. 3. pp. 249-258.
Luger et al, "Correct Folding of Circularly Permuted Variants of a Ba Barrel Enzyme in Vivo", Science, vol. 243.
Luger et al, An 8 fold Ba Barrel Protein with Redundant Folding Possibilities , Protein Engineering, vol. 3. pp. 249 258. *
Luger et al, Correct Folding of Circularly Permuted Variants of a Ba Barrel Enzyme in Vivo , Science, vol. 243. *
MacGregor et al, "A circularly permuted a-amylase-type", FEBS Letters, 1996, vol. 378, pp. 263-266.
MacGregor et al, A circularly permuted a amylase type , FEBS Letters, 1996, vol. 378, pp. 263 266. *
Mullins et al. "Transposition of Protein Sequences: Circular Permutation of Ribonuclease T1", J. Am. Chem. Soc., 1994, vol. 116, pp. 5529-5533.
Mullins et al. Transposition of Protein Sequences: Circular Permutation of Ribonuclease T1 , J. Am. Chem. Soc., 1994, vol. 116, pp. 5529 5533. *
Protasova et al, Circularly permuted dihydrofolate reductase of E. coli has functional activity and a destabilized tertiary structure:, Protein Engineering, 1994, vol. 7, No. 11, pp. 1373 1777. *
Protasova et al, Circularly permuted dihydrofolate reductase of E. coli has functional activity and a destabilized tertiary structure:, Protein Engineering, 1994, vol. 7, No. 11, pp. 1373-1777.
Reeke et al., "Three-Dimensional Structure of Favin: Saccharide Binding-Cyclic Permutation in Leguminous Lectins", Science, Nov. 28, 1986, vol. 234 pp. 1108-1111.
Reeke et al., Three Dimensional Structure of Favin: Saccharide Binding Cyclic Permutation in Leguminous Lectins , Science, Nov. 28, 1986, vol. 234 pp. 1108 1111. *
Ritco et al, "Is the Continuity of the Domains Required for the Correct Folding of a Two-Domain Protein?", Biochemistry, 1995, vol. 34, pp. 16543-16551.
Ritco et al, Is the Continuity of the Domains Required for the Correct Folding of a Two Domain Protein , Biochemistry, 1995, vol. 34, pp. 16543 16551. *
Vignai et al, "Circular permutation within the coenzyme binding domain of the tetrameric glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus", Protein Science, 1995, vol. 4, pp. 994-1000.
Vignai et al, Circular permutation within the coenzyme binding domain of the tetrameric glyceraldehyde 3 phosphate dehydrogenase from Bacillus stearothermophilus , Protein Science, 1995, vol. 4, pp. 994 1000. *
Viguera et al, "The order of secondary structure elements", J. Mol. Biol., 1995, vol. 247, pp. 670-681.
Viguera et al, The order of secondary structure elements , J. Mol. Biol., 1995, vol. 247, pp. 670 681. *
Watanabe et al, "Mutant Protein of Recombinant Human Granulocyte Colony-Stimulating Factor . . . ", Analytical Biochemistry, 1991, vol. 195 pp. 38-44.
Watanabe et al, Mutant Protein of Recombinant Human Granulocyte Colony Stimulating Factor . . . , Analytical Biochemistry, 1991, vol. 195 pp. 38 44. *
Yang et al, "Aspartate transcarbamoylase containing circularly permuted catalytic polypeptide chains", Proc. Natl. Acad. Sci. USA, 1993, vol. 90, pp. 11980-11984.
Yang et al, Aspartate transcarbamoylase containing circularly permuted catalytic polypeptide chains , Proc. Natl. Acad. Sci. USA, 1993, vol. 90, pp. 11980 11984. *
Zhang et al, "Circular Permutation of T4 Lysozyme", Biochemistry, vol. 32, No. 46, 1993.
Zhang et al, Circular Permutation of T4 Lysozyme , Biochemistry, vol. 32, No. 46, 1993. *

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7381804B2 (en) 1993-01-28 2008-06-03 Amgen Inc. G-CSF analog compositions and methods
US20030171559A1 (en) * 1993-01-28 2003-09-11 Amgen Inc. G-CSF analog compositions and methods
US6632426B2 (en) 1993-01-28 2003-10-14 Amgen Inc. G-CSF analog compositions and methods
US8058398B2 (en) 1993-01-28 2011-11-15 Amgen Inc. Modified G-CSF polypeptide
US6261550B1 (en) 1993-01-28 2001-07-17 Amgen Inc. G-CSF hybrid molecules and pharmaceutical compositions
US20050260154A1 (en) * 1993-01-28 2005-11-24 Amgen Inc. G-CSF analog compositions and methods
US7696153B2 (en) 2000-01-10 2010-04-13 Maxygen, Inc. G-CSF conjugates
US7550565B2 (en) 2000-01-10 2009-06-23 Maxygen Holdings Ltd. G-CSF conjugates
US20070010660A1 (en) * 2000-01-10 2007-01-11 Maxygen Holdings, Ltd. G-CSF Conjugates
US20060286069A1 (en) * 2000-01-10 2006-12-21 Maxygen Holdings, Ltd. G-CSF Conjugates
US20050095684A1 (en) * 2000-01-10 2005-05-05 Maxygen Holdings Ltd. G-CSF conjugates
US20060084793A1 (en) * 2000-01-10 2006-04-20 Maxygen Holdings, Ltd. G-CSF polypeptides and conjugates
US7550566B2 (en) 2000-01-10 2009-06-23 Maxygen Holdings Ltd. G-CSF conjugates
US20040028661A1 (en) * 2002-08-07 2004-02-12 Bartelmez Stephen H. Expansion of cells using thrombopoietin and anti-transforming growth factor-beta
US20070196911A1 (en) * 2004-07-12 2007-08-23 Giovanni Mambrini Devices and methods for growing human cells
US7655766B2 (en) 2005-06-01 2010-02-02 Carsten Germansen Compositions comprising positional isomers of PEGylated G-CSF
US7381805B2 (en) 2005-06-01 2008-06-03 Maxygen Holdings, Ltd. Compositions comprising mixtures of positional PEG isomers of PEGylated G-CSF
US9181531B2 (en) 2011-12-21 2015-11-10 Apse, Llc Process for purifying VLPs
EP4019636A1 (en) 2011-12-21 2022-06-29 Apse Llc Processes using vlps with capsids resistant to hydrolases
EP3222274A1 (en) 2013-06-19 2017-09-27 Apse Llc Compositions and methods using capsids resistant to hydrolases
US9822361B2 (en) 2013-06-19 2017-11-21 Apse, Inc. Compositions and methods using capsids resistant to hydrolases
EP3789017A1 (en) 2013-06-19 2021-03-10 Apse Llc Compositions and methods using capsids resistant to hydrolases

Also Published As

Publication number Publication date
US6730303B1 (en) 2004-05-04
US20040171115A1 (en) 2004-09-02

Similar Documents

Publication Publication Date Title
US6066318A (en) Multi-functional hematopoietic fusion proteins between sequence rearranged C-MPL receptor agonists and other hematopoietic factors
US6436387B1 (en) Methods of ex-vivo expansion of hematopoietic cells using multivariant IL-3 hematopoiesis chimera proteins
AU705083B2 (en) Multi-functional hematopoietic receptor agonists
AU725547B2 (en) Multi-functional chimeric hematopoietic receptor agonists
US6100070A (en) G-CSF receptor agonists
WO1997012985A9 (en) Multi-functional hematopoietic receptor agonists
CA2268027A1 (en) Novel flt-3 receptor agonists
AU717733B2 (en) Novel G-CSF receptor agonists
US20070081979A1 (en) Multi-functional chimeric hematopoietic receptor agonists
AU7390196A (en) Novel c-mpl receptor agonists
NZ337911A (en) flt3 ligand chimeric proteins
AU703627B2 (en) Interleuken-3 (IL-3) receptor agonists
MXPA99003877A (en) Multi-functional chimeric hematopoietic receptor agonists
MXPA99003875A (en) NOVEL flt-3 RECEPTOR AGONISTS

Legal Events

Date Code Title Description
AS Assignment

Owner name: G.D. SEARLE & CO., ILLINOIS

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:FENG, YIQING;STATEN, NICHOLAS R.;BAUM, CHARLES M.;AND OTHERS;REEL/FRAME:008808/0636;SIGNING DATES FROM 19971010 TO 19971017

AS Assignment

Owner name: G.D. SEARLE & CO., ILLINOIS

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:YINING, FENG;CAPARON, M.;ZURFLUH, L.;AND OTHERS;REEL/FRAME:009086/0412;SIGNING DATES FROM 19970416 TO 19970425

FEPP Fee payment procedure

Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

FPAY Fee payment

Year of fee payment: 4

REMI Maintenance fee reminder mailed
LAPS Lapse for failure to pay maintenance fees
STCH Information on status: patent discontinuation

Free format text: PATENT EXPIRED DUE TO NONPAYMENT OF MAINTENANCE FEES UNDER 37 CFR 1.362

FP Lapsed due to failure to pay maintenance fee

Effective date: 20080523